Mechanisms of ribosomopathy and phase separation-related ribosomopathy

Zhiyuan PAN; Guofen LIN; Hao LIU; Guozhi LI; Xiaoyi ZHANG; Jiewen DAI

doi:10.1631/jzus.B2300904

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Review | Updated：2025-06-24

Mechanisms of ribosomopathy and phase separation-related ribosomopathy
Mechanisms of ribosomopathy and phase separation-related ribosomopathy
核糖体病和相分离相关核糖体病的机制
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 6, Pages: 503-526(2025)
Affiliations：

1.Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
2.Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
3.School of Stomatology, Shandong Second Medical University, Weifang 261000, China
4.Orthopedic and Reconstructive Medicine Center, The First Affiliated Hospital of Ningbo University, Ningbo 315211, China
Funds：
DOI：10.1631/jzus.B2300904
CLC：
CSTR：
Received：11 December 2023，

Revised：24 April 2024，

Published Online：02 June 2025，

Published：24 June 2025
Accepted：

潘祉源,林国芬,刘昊等.核糖体病和相分离相关核糖体病的机制[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(06):503-526.

Zhiyuan PAN, Guofen LIN, Hao LIU, et al. Mechanisms of ribosomopathy and phase separation-related ribosomopathy[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(6): 503-526.
潘祉源,林国芬,刘昊等.核糖体病和相分离相关核糖体病的机制[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(06):503-526. DOI： 10.1631/jzus.B2300904.

Zhiyuan PAN, Guofen LIN, Hao LIU, et al. Mechanisms of ribosomopathy and phase separation-related ribosomopathy[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(6): 503-526. DOI： 10.1631/jzus.B2300904.

摘要

核糖体是细胞内的核糖核蛋白颗粒，是蛋白质生物合成的场所。编码核糖体蛋白（RP）和核糖体生物发生因子（RBF）的基因突变会导致核糖体功能障碍，从而引发一系列疾病，统称为核糖体病。相分离是一种从均质混合物中产生多相的热力学过程。无膜细胞器和细胞内结构（包括核糖体和核小体）的形成离不开相分离现象的参与。本文系统综述了核糖体的结构、生物发生及其与核糖体病的关系，特别讨论了核糖体病的组织特异性和相分离在其中的作用机制。这些发现为理解核糖体病的发病机理提供重要线索，并为进一步开展核糖体病预防、诊断和治疗提供了新思路。

Abstract

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases

collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures

including ribosomes and nucleoli

cannot occur without the involvement of phase separation. Here

ribosome structure

biogenesis

and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed

which may offer some clues for understanding the mechanisms of ribosomopathy. Then

some new ideas for the prevention

diagnosis

and treatment of ribosomopathy are provided.

关键词

Keywords

references

Abdulhadi-Atwan M , Klopstock T , Sharaf M , et al. , 2020 . The novel R211Q POP1 homozygous mutation causes different pathogenesis and skeletal changes from those of previously reported POP1 -associated anauxetic dysplasia . Am J Med Genet A , 182 ( 5 ): 1268 - 1272 . https://doi.org/10.1002/ajmg.a.61538 https://doi.org/10.1002/ajmg.a.61538

Achilleos A , Trainor PA , 2015 . Mouse models of rare craniofacial disorders . Curr Top Dev Biol , 115 : 413 - 458 . https://doi.org/10.1016/bs.ctdb.2015.07.011 https://doi.org/10.1016/bs.ctdb.2015.07.011

Ambekar C , Das B , Yeger H , et al. , 2010 . SBDS-deficiency results in deregulation of reactive oxygen species leading to increased cell death and decreased cell growth . Pediatr Blood Cancer , 55 ( 6 ): 1138 - 1144 . https://doi.org/10.1002/pbc.22700 https://doi.org/10.1002/pbc.22700

Amsterdam A , Nissen RM , Sun ZX , et al. , 2004 . Identification of 315 genes essential for early zebrafish development . Proc Natl Acad Sci USA , 101 ( 35 ): 12792 - 12797 . https://doi.org/10.1073/pnas.0403929101 https://doi.org/10.1073/pnas.0403929101

An K , Zhou JB , Xiong Y , et al. , 2021 . Computational studies of the structural basis of human RPS19 mutations associated with Diamond-Blackfan Anemia . Front Genet , 12 : 650897 . https://doi.org/10.3389/fgene.2021.650897 https://doi.org/10.3389/fgene.2021.650897

Anderson SJ , Lauritsen JPH , Hartman MG , et al. , 2007 . Ablation of ribosomal protein L22 selectively impairs αβ T cell development by activation of a p53-dependent checkpoint . Immunity , 26 ( 6 ): 759 - 772 . https://doi.org/10.1016/j.immuni.2007.04.012 https://doi.org/10.1016/j.immuni.2007.04.012

Balogh E , Chandler JC , Varga M , et al. , 2020 . Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis . Proc Natl Acad Sci USA , 117 ( 26 ): 15137 - 15147 . https://doi.org/10.1073/pnas.2002328117 https://doi.org/10.1073/pnas.2002328117

Banani SF , Lee HO , Hyman AA , et al. , 2017 . Biomolecular condensates: organizers of cellular biochemistry . Nat Rev Mol Cell Biol , 18 ( 5 ): 285 - 298 . https://doi.org/10.1038/nrm.2017.7 https://doi.org/10.1038/nrm.2017.7

Barraza-García J , Rivera-Pedroza CI , Hisado-Oliva A , et al. , 2017 . Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia . Clin Genet , 92 ( 1 ): 91 - 98 . https://doi.org/10.1111/cge.12964 https://doi.org/10.1111/cge.12964

Baßler J , Hurt E , 2019 . Eukaryotic ribosome assembly . Annu Rev Biochem , 88 : 281 - 306 . https://doi.org/10.1146/annurev-biochem-013118-110817 https://doi.org/10.1146/annurev-biochem-013118-110817

Belin S , Beghin A , Solano-Gonzàlez E , et al. , 2009 . Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells . PLoS ONE , 4 ( 9 ): e7147 . https://doi.org/10.1371/journal.pone.0007147 https://doi.org/10.1371/journal.pone.0007147

Bezzerri V , Cipolli M , 2019 . Shwachman-Diamond syndrome: molecular mechanisms and current perspectives . Mol Diagn Ther , 23 ( 2 ): 281 - 290 . https://doi.org/10.1007/s40291-018-0368-2 https://doi.org/10.1007/s40291-018-0368-2

Bhat P , Honson D , Guttman M , 2021 . Nuclear compartmentalization as a mechanism of quantitative control of gene expression . Nat Rev Mol Cell Biol , 22 ( 10 ): 653 - 670 . https://doi.org/10.1038/s41580-021-00387-1 https://doi.org/10.1038/s41580-021-00387-1

Boisvert FM , Lamond AI , 2010 . p53-Dependent subcellular proteome localization following DNA damage . Proteomics , 10 ( 22 ): 4087 - 4097 . https://doi.org/10.1002/pmic.201000213 https://doi.org/10.1002/pmic.201000213

Boisvert FM , van Koningsbruggen S , Navascués J , et al. , 2007 . The multifunctional nucleolus . Nat Rev Mol Cell Biol , 8 ( 7 ): 574 - 585 . https://doi.org/10.1038/nrm2184 https://doi.org/10.1038/nrm2184

Bolze A , Mahlaoui N , Byun M , et al. , 2013 . Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia . Science , 340 ( 6135 ): 976 - 978 . https://doi.org/10.1126/science.1234864 https://doi.org/10.1126/science.1234864

Boulon S , Westman BJ , Hutten S , et al. , 2010 . The nucleolus under stress . Mol Cell , 40 ( 2 ): 216 - 227 . https://doi.org/10.1016/j.molcel.2010.09.024 https://doi.org/10.1016/j.molcel.2010.09.024

Boultwood J , Pellagatti A , McKenzie ANJ , et al. , 2010 . Advances in the 5q- syndrome . Blood , 116 ( 26 ): 5803 - 5811 . https://doi.org/10.1182/blood-2010-04-273771 https://doi.org/10.1182/blood-2010-04-273771

Bourque DK , Hartley T , Nikkel SM , et al. , 2018 . A de novo mutation in RPL10 causes a rare X-linked ribosomopathy characterized by syndromic intellectual disability and epilepsy: a new case and review of the literature . Eur J Med Genet , 61 ( 2 ): 89 - 93 . https://doi.org/10.1016/j.ejmg.2017.10.011 https://doi.org/10.1016/j.ejmg.2017.10.011

Box JK , Paquet N , Adams MN , et al. , 2016 . Nucleophosmin: from structure and function to disease development . BMC Mol Biol , 17 : 19 . https://doi.org/10.1186/s12867-016-0073-9 https://doi.org/10.1186/s12867-016-0073-9

Brooks SS , Wall AL , Golzio C , et al. , 2014 . A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans . Genetics , 198 ( 2 ): 723 - 733 . https://doi.org/10.1534/genetics.114.168211 https://doi.org/10.1534/genetics.114.168211

Burroughs L , Woolfrey A , Shimamura A , 2009 . Shwachman-diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment . Hematol Oncol Clin North Am , 23 ( 2 ): 233 - 248 . https://doi.org/10.1016/j.hoc.2009.01.007 https://doi.org/10.1016/j.hoc.2009.01.007

Cai DF , Feliciano D , Dong P , et al. , 2019 . Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression . Nat Cell Biol , 21 ( 12 ): 1578 - 1589 . https://doi.org/10.1038/s41556-019-0433-z https://doi.org/10.1038/s41556-019-0433-z

Cai PC , Mao XY , Zhao JQ , et al. , 2018 . Ribosome biogenesis protein Urb2 regulates hematopoietic stem cells development via P53 pathway in zebrafish . Biochem Biophys Res Commun , 497 ( 2 ): 776 - 782 . https://doi.org/10.1016/j.bbrc.2018.02.153 https://doi.org/10.1016/j.bbrc.2018.02.153

Calo E , Gu B , Bowen ME , et al. , 2018 . Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders . Nature , 554 ( 7690 ): 112 - 117 . https://doi.org/10.1038/nature25449 https://doi.org/10.1038/nature25449

Cao PB , Yang AQ , Li PY , et al. , 2021 . Genomic gain of RRS1 promotes hepatocellular carcinoma through reducing the RPL11-MDM2-p53 signaling . Sci Adv , 7 ( 35 ): eabf4304 . https://doi.org/10.1126/sciadv.abf4304 https://doi.org/10.1126/sciadv.abf4304

Chagnon P , Michaud J , Mitchell G , et al. , 2002 . A missense mutation (R565W) in Cirhin (FLJ14728) in North American Indian childhood cirrhosis . Am J Hum Genet , 71 ( 6 ): 1443 - 1449 . https://doi.org/10.1086/344580 https://doi.org/10.1086/344580

Chakraborty A , Uechi T , Higa S , et al. , 2009 . Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response . PLoS ONE , 4 ( 1 ): e4152 . https://doi.org/10.1371/journal.pone.0004152 https://doi.org/10.1371/journal.pone.0004152

Chen J , Guo KX , Kastan MB , 2012 . Interactions of nucleolin and ribosomal protein L26 (RPL26) in translational control of human p53 mRNA . J Biol Chem , 287 ( 20 ): 16467 - 16476 . https://doi.org/10.1074/jbc.M112.349274 https://doi.org/10.1074/jbc.M112.349274

Chen J , Crutchley J , Zhang DD , et al. , 2017 . Identification of a DNA damage-induced alternative splicing pathway that regulates p53 and cellular senescence markers . Cancer Discov , 7 ( 7 ): 766 - 781 . https://doi.org/10.1158/2159-8290.CD-16-0908 https://doi.org/10.1158/2159-8290.CD-16-0908

Chen XD , Wu XD , Wu HW , et al. , 2020 . Phase separation at the synapse . Nat Neurosci , 23 ( 3 ): 301 - 310 . https://doi.org/10.1038/s41593-019-0579-9 https://doi.org/10.1038/s41593-019-0579-9

Cheng Z , Mugler CF , Keskin A , et al. , 2019 . Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate . Mol Cell , 73 ( 1 ): 36 - 47.e10 . https://doi.org/10.1016/j.molcel.2018.10.032 https://doi.org/10.1016/j.molcel.2018.10.032

da Costa L , Leblanc T , Mohandas N , 2020 . Diamond-Blackfan anemia . Blood , 136 ( 11 ): 1262 - 1273 . https://doi.org/10.1182/blood.2019000947 https://doi.org/10.1182/blood.2019000947

Dash S , Trainor PA , 2022 . Nucleolin loss of function leads to aberrant fibroblast growth factor signaling and craniofacial anomalies . Development , 149 ( 12 ): dev200349 . https://doi.org/10.1242/dev.200349 https://doi.org/10.1242/dev.200349

Dauwerse JG , Dixon J , Seland S , et al. , 2011 . Mutations in genes encoding subunits of RNA polymerases I and III cause treacher collins syndrome . Nat Genet , 43 ( 1 ): 20 - 22 . https://doi.org/10.1038/ng.724 https://doi.org/10.1038/ng.724

de Keersmaecker K , Atak ZK , Li N , et al. , 2013 . Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia . Nat Genet , 45 ( 2 ): 186 - 190 . https://doi.org/10.1038/ng.2508 https://doi.org/10.1038/ng.2508

Decatur WA , Fournier MJ , 2003 . RNA-guided nucleotide modification of ribosomal and other RNAs . J Biol Chem , 278 ( 2 ): 695 - 698 . https://doi.org/10.1074/jbc.R200023200 https://doi.org/10.1074/jbc.R200023200

de la Cruz J , Karbstein K , Woolford JL , 2015 . Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo . Annu Rev Biochem , 84 : 93 - 129 . https://doi.org/10.1146/annurev-biochem-060614-033917 https://doi.org/10.1146/annurev-biochem-060614-033917

Delhermite J , Tafforeau L , Sharma S , et al. , 2022 . Systematic mapping of rRNA 2'-O methylation during frog development and involvement of the methyltransferase Fibrillarin in eye and craniofacial development in Xenopus laevis . PLoS Genet , 18 ( 1 ): e1010012 . https://doi.org/10.1371/journal.pgen.1010012 https://doi.org/10.1371/journal.pgen.1010012

Dharia AP , Obla A , Gajdosik MD , et al. , 2014 . Tempo and mode of gene duplication in mammalian ribosomal protein evolution . PLoS ONE , 9 ( 11 ): e111721 . https://doi.org/10.1371/journal.pone.0111721 https://doi.org/10.1371/journal.pone.0111721

Dixon J , Jones NC , Sandell LL , et al. , 2006 . Tcof1 /Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities . Proc Natl Acad Sci USA , 103 ( 36 ): 13403 - 13408 . https://doi.org/10.1073/pnas.0603730103 https://doi.org/10.1073/pnas.0603730103

Dixon MJ , 1995 . Treacher Collins syndrome . J Med Genet , 32 ( 10 ): 806 - 808 . https://doi.org/10.1136/jmg.32.10.806 https://doi.org/10.1136/jmg.32.10.806

Donati G , Bertoni S , Brighenti E , et al. , 2011 . The balance between rRNA and ribosomal protein synthesis up- and downregulates the tumour suppressor p53 in mammalian cells . Oncogene , 30 ( 29 ): 3274 - 3288 . https://doi.org/10.1038/onc.2011.48 https://doi.org/10.1038/onc.2011.48

Dorn KM , Burns KD , Trout MAR , et al. , 2021 . Diamond-Blackfan anemia: a case report and review of the literature . Neonatology , 118 ( 4 ): 500 - 504 . https://doi.org/10.1159/000516030 https://doi.org/10.1159/000516030

Dror Y , 2005 . Shwachman-Diamond syndrome . Pediatr Blood Cancer , 45 ( 7 ): 892 - 901 . https://doi.org/10.1002/pbc.20478 https://doi.org/10.1002/pbc.20478

Drouin E , Russo P , Tuchweber B , et al. , 2000 . North American Indian cirrhosis in children: a review of 30 cases . J Pediatr Gastroenterol Nutr , 31 ( 4 ): 395 - 404 . https://doi.org/10.1097/00005176-200010000-00013 https://doi.org/10.1097/00005176-200010000-00013

Dutt S , Narla A , Lin K , et al. , 2011 . Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells . Blood , 117 ( 9 ): 2567 - 2576 . https://doi.org/10.1182/blood-2010-07-295238 https://doi.org/10.1182/blood-2010-07-295238

Ear J , Hsueh J , Nguyen M , et al. , 2016 . A zebrafish model of 5q-syndrome using CRISPR/Cas9 targeting RPS14 reveals a p53-independent and p53-dependent mechanism of erythroid failure . J Genet Genomics , 43 ( 5 ): 307 - 318 . https://doi.org/10.1016/j.jgg.2016.03.007 https://doi.org/10.1016/j.jgg.2016.03.007

Ebert BL , Pretz J , Bosco J , et al. , 2008 . Identification of RPS14 as a 5q - syndrome gene by RNA interference screen . Nature , 451 ( 7176 ): 335 - 339 . https://doi.org/10.1038/nature06494 https://doi.org/10.1038/nature06494

Elalaoui SC , Laarabi FZ , Mansouri M , et al. , 2016 . Further evidence of POP1 mutations as the cause of anauxetic dysplasia . Am J Med Genet A , 170 ( 9 ): 2462 - 2465 . https://doi.org/10.1002/ajmg.a.37839 https://doi.org/10.1002/ajmg.a.37839

Engeland K , 2018 . Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM . Cell Death Differ , 25 ( 1 ): 114 - 132 . https://doi.org/10.1038/cdd.2017.172 https://doi.org/10.1038/cdd.2017.172

Falcon KT , Watt KEN , Dash S , et al. , 2022 . Dynamic regulation and requirement for ribosomal RNA transcription during mammalian development . Proc Natl Acad Sci USA , 119 ( 31 ): e2116974119 . https://doi.org/10.1073/pnas.2116974119 https://doi.org/10.1073/pnas.2116974119

Farley-Barnes KI , Ogawa LM , Baserga SJ , 2019 . Ribosomopathies: old concepts, new controversies . Trends Genet , 35 ( 10 ): 754 - 767 . https://doi.org/10.1016/j.tig.2019.07.004 https://doi.org/10.1016/j.tig.2019.07.004

Farrar JE , Vlachos A , Atsidaftos E , et al. , 2011 . Ribosomal protein gene deletions in Diamond-Blackfan anemia . Blood , 118 ( 26 ): 6943 - 6951 . https://doi.org/10.1182/blood-2011-08-375170 https://doi.org/10.1182/blood-2011-08-375170

Feng LF , Du J , Yao CJ , et al. , 2020 . Ribosomal DNA copy number is associated with p53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients . Environ Int , 138 : 105593 . https://doi.org/10.1016/j.envint.2020.105593 https://doi.org/10.1016/j.envint.2020.105593

Feric M , Vaidya N , Harmon TS , et al. , 2016 . Coexisting liquid phases underlie nucleolar subcompartments . Cell , 165 ( 7 ): 1686 - 1697 . https://doi.org/10.1016/j.cell.2016.04.047 https://doi.org/10.1016/j.cell.2016.04.047

Ferretti MB , Karbstein K , 2019 . Does functional specialization of ribosomes really exist? RNA , 25 ( 5 ): 521 - 538 . https://doi.org/10.1261/rna.069823.118 https://doi.org/10.1261/rna.069823.118

Ferretti MB , Ghalei H , Ward EA , et al. , 2017 . Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements . Nat Struct Mol Biol , 24 ( 9 ): 700 - 707 . https://doi.org/10.1038/nsmb.3442 https://doi.org/10.1038/nsmb.3442

Filbeck S , Cerullo F , Pfeffer S , et al. , 2022 . Ribosome-associated quality-control mechanisms from bacteria to humans . Mol Cell , 82 ( 8 ): 1451 - 1466 . https://doi.org/10.1016/j.molcel.2022.03.038 https://doi.org/10.1016/j.molcel.2022.03.038

Flygare J , Karlsson S , 2007 . Diamond-Blackfan anemia: erythropoiesis lost in translation . Blood , 109 ( 8 ): 3152 - 3154 . https://doi.org/10.1182/blood-2006-09-001222 https://doi.org/10.1182/blood-2006-09-001222

Freed EF , Prieto JL , McCann KL , et al. , 2012 . NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing . PLoS Genet , 8 ( 8 ): e1002892 . https://doi.org/10.1371/journal.pgen.1002892 https://doi.org/10.1371/journal.pgen.1002892

Frottin F , Schueder F , Tiwary S , et al. , 2019 . The nucleolus functions as a phase-separated protein quality control compartment . Science , 365 ( 6451 ): 342 - 347 . https://doi.org/10.1126/science.aaw9157 https://doi.org/10.1126/science.aaw9157

Fujioka Y , Noda NN , 2021 . Biomolecular condensates in autophagy regulation . Curr Opin Cell Biol , 69 : 23 - 29 . https://doi.org/10.1016/j.ceb.2020.12.011 https://doi.org/10.1016/j.ceb.2020.12.011

Gabryelczyk B , Cai H , Shi XY , et al. , 2019 . Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides . Nat Commun , 10 : 5465 . https://doi.org/10.1038/s41467-019-13469-8 https://doi.org/10.1038/s41467-019-13469-8

Ganapathi KA , Shimamura A , 2008 . Ribosomal dysfunction and inherited marrow failure . Br J Haematol , 141 ( 3 ): 376 - 387 . https://doi.org/10.1111/j.1365-2141.2008.07095.x https://doi.org/10.1111/j.1365-2141.2008.07095.x

Gay DM , Lund AH , Jansson MD , 2022 . Translational control through ribosome heterogeneity and functional specialization . Trends Biochem Sci , 47 ( 1 ): 66 - 81 . https://doi.org/10.1016/j.tibs.2021.07.001 https://doi.org/10.1016/j.tibs.2021.07.001

Genuth NR , Barna M , 2018 . The discovery of ribosome heterogeneity and its implications for gene regulation and organismal life . Mol Cell , 71 ( 3 ): 364 - 374 . https://doi.org/10.1016/j.molcel.2018.07.018 https://doi.org/10.1016/j.molcel.2018.07.018

Gibson BA , Doolittle LK , Schneider MWG , et al. , 2019 . Organization of chromatin by intrinsic and regulated phase separation . Cell , 179 ( 2 ): 470 - 484.e21 . https://doi.org/10.1016/j.cell.2019.08.037 https://doi.org/10.1016/j.cell.2019.08.037

Gonzales B , Henning D , So RB , et al. , 2005 . The Treacher collins syndrome ( TCOF1 ) gene product is involved in pre-rRNA methylation . Hum Mol Genet , 14 ( 14 ): 2035 - 2043 . https://doi.org/10.1093/hmg/ddi208 https://doi.org/10.1093/hmg/ddi208

Gopanenko AV , Kolobova AV , Tupikin AE , et al. , 2021 . Knockdown of the ribosomal protein eL38 in HEK293 cells changes the translational efficiency of specific genes . Int J Mol Sci , 22 ( 9 ): 4531 . https://doi.org/10.3390/ijms22094531 https://doi.org/10.3390/ijms22094531

Griffin JN , Sondalle SB , del Viso F , et al. , 2015 . The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus . PLoS Genet , 11 ( 3 ): e1005018 . https://doi.org/10.1371/journal.pgen.1005018 https://doi.org/10.1371/journal.pgen.1005018

Gripp KW , Curry C , Olney AH , et al. , 2014 . Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28 . Am J Med Genet A , 164 ( 9 ): 2240 - 2249 . https://doi.org/10.1002/ajmg.a.36633 https://doi.org/10.1002/ajmg.a.36633

Grzanka M , Piekiełko-Witkowska A , 2021 . The role of TCOF1 gene in health and disea se: beyond Treacher Collins syndrome . Int J Mol Sci , 22 ( 5 ): 2482 . https://doi.org/10.3390/ijms22052482 https://doi.org/10.3390/ijms22052482

Guillen-Chable F , Corona UR , Pereira-Santana A , et al. , 2020 . Fibrillarin ribonuclease activity is dependent on the GAR domain and modulated by phospholipids . Cells , 9 ( 5 ): 1143 . https://doi.org/10.3390/cells9051143 https://doi.org/10.3390/cells9051143

Hernández Borrero LJ , El-Deiry WS , 2021 . Tumor suppressor p53: biology, signaling pathways, and therapeutic targeting . Biochim Biophys Acta Rev Cancer , 1876 ( 1 ): 188556 . https://doi.org/10.1016/j.bbcan.2021.188556 https://doi.org/10.1016/j.bbcan.2021.188556

Hernandez-Verdun D , Roussel P , Thiry M , et al. , 2010 . The nucleolus: structure/function relationship in RNA metabolism . WIREs RNA , 1 ( 3 ): 415 - 431 . https://doi.org/10.1002/wrna.39 https://doi.org/10.1002/wrna.39

Hindley A , Catherwood MA , McMullin MF , et al. , 2021 . Significance of NPM1 gene mutations in AML . Int J Mol Sci , 22 ( 18 ): 10040 . https://doi.org/10.3390/ijms221810040 https://doi.org/10.3390/ijms221810040

Hiraoka Y , 2020 . Phase separation drives pairing of homologous chromosomes . Curr Genet , 66 ( 5 ): 881 - 887 . https://doi.org/10.1007/s00294-020-01077-9 https://doi.org/10.1007/s00294-020-01077-9

Holmberg Olausson K , Nistér M , Lindström MS , 2012 . P53-dependent and -independent nucleolar stress responses . Cells , 1 ( 4 ): 774 - 798 . https://doi.org/10.3390/cells1040774 https://doi.org/10.3390/cells1040774

Hondele M , Heinrich S , de Los Rios P , et al. , 2020 . Membraneless organelles: phasing out of equilibrium . Emerg Top Life Sci , 4 ( 3 ): 343 - 354 . https://doi.org/10.1042/ETLS20190190 https://doi.org/10.1042/ETLS20190190

Hunter AGW , Woerner SJ , Montalvo-Hicks LDC , et al. , 1979 . The Bowen-Conradi syndrome—a highly lethal autosomal recessive syndrome of microcephaly, micrognathia, low birth weight, and joint deformities . Am J Med Genet , 3 ( 3 ): 269 - 279 . https://doi.org/10.1002/ajmg.1320030305 https://doi.org/10.1002/ajmg.1320030305

Ide S , Imai R , Ochi H , et al. , 2020 . Transcriptional suppression of ribosomal DNA with phase separation . Sci Adv , 6 ( 42 ): eabb5953 . https://doi.org/10.1126/sciadv.abb5953 https://doi.org/10.1126/sciadv.abb5953

Iida T , Kobayashi T , 2019 . How do cells count multi-copy genes?: “Musical Chair” model for preserving the number of rDNA copies . Curr Genet , 65 ( 4 ): 883 - 885 . https://doi.org/10.1007/s00294-019-00956-0 https://doi.org/10.1007/s00294-019-00956-0

Jia WY , Yao ZY , Zhao JJ , et al. , 2017 . New perspectives of physiological and pathological functions of nucleolin (NCL) . Life Sci , 186 : 1 - 10 . https://doi.org/10.1016/j.lfs.2017.07.025 https://doi.org/10.1016/j.lfs.2017.07.025

Jobe A , Liu Z , Gutierrez-Vargas C , et al. , 2019 . New insights into ribosome structure and function . Cold Spring Harb Perspect Biol , 11 ( 1 ): a032615 . https://doi.org/10.1101/cshperspect.a032615 https://doi.org/10.1101/cshperspect.a032615

Jones NC , Lynn ML , Gaudenz K , et al. , 2008 . Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function . Nat Med , 14 ( 2 ): 125 - 133 . https://doi.org/10.1038/nm1725 https://doi.org/10.1038/nm1725

Jyonouchi S , Forbes L , Ruchelli E , et al. , 2011 . Dyskeratosis congenita: a combined immunodeficiency with broad clinical spectrum ‒ a single-center pediatric experience . Pediatr Allergy Immunol , 22 ( 3 ): 313 - 319 . https://doi.org/10.1111/j.1399-3038.2010.01136.x https://doi.org/10.1111/j.1399-3038.2010.01136.x

Kang J , Brajanovski N , Chan KT , et al. , 2021 . Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy . Signal Transduct Target Ther , 6 : 323 . https://doi.org/10.1038/s41392-021-00728-8 https://doi.org/10.1038/s41392-021-00728-8

Khatter H , Myasnikov AG , Natchiar SK , et al. , 2015 . Structure of the human 80S ribosome . Nature , 520 ( 7549 ): 640 - 645 . https://doi.org/10.1038/nature14427 https://doi.org/10.1038/nature14427

Killen MW , Stults DM , Adachi N , et al. , 2009 . Loss of Bloom syndrome protein destabilizes human gene cluster architecture . Hum Mol Genet , 18 ( 18 ): 3417 - 3428 . https://doi.org/10.1093/hmg/ddp282 https://doi.org/10.1093/hmg/ddp282

Klauck SM , Felder B , Kolb-Kokocinski A , et al. , 2006 . Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism . Mol Psychiatry , 11 ( 12 ): 1073 - 1084 . https://doi.org/10.1038/sj.mp.4001883 https://doi.org/10.1038/sj.mp.4001883

Klinge S , Voigts-Hoffmann F , Leibundgut M , et al. , 2011 . Crystal structure of the eukaryotic 60 S ribosomal subunit in complex with initiation factor 6 . Science , 334 ( 6058 ): 941 - 948 . https://doi.org/10.1126/science.1211204 https://doi.org/10.1126/science.1211204

Koch S , Garcia Gonzalez O , Assfalg R , et al. , 2014 . Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth . Cell Cycle , 13 ( 13 ): 2029 - 2037 . https://doi.org/10.4161/cc.29018 https://doi.org/10.4161/cc.29018

Kondrashov N , Pusic A , Stumpf CR , et al. , 2011 . Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning . Cell , 145 ( 3 ): 383 - 397 . https://doi.org/10.1016/j.cell.2011.03.028 https://doi.org/10.1016/j.cell.2011.03.028

Kovacevic J , Palm D , Jooss D , et al. , 2019 . Co-orthologues of ribosome biogenesis factors in A. thaliana are differentially regulated by transcription factors . Plant Cell Rep , 38 ( 8 ): 937 - 949 . https://doi.org/10.1007/s00299-019-02416-y https://doi.org/10.1007/s00299-019-02416-y

Kwong EML , Ho JCH , Lau MCC , et al. , 2018 . Restoration of polr1c in early embryogenesis rescues the type 3 treacher collins syndrome facial malformation phenotype in zebrafish . Am J Pathol , 188 ( 2 ): 336 - 342 . https://doi.org/10.1016/j.ajpath.2017.10.004 https://doi.org/10.1016/j.ajpath.2017.10.004

Lafontaine DLJ , Riback JA , Bascetin R , et al. , 2021 . The nucleolus as a multiphase liquid condensate . Nat Rev Mol Cell Biol , 22 ( 3 ): 165 - 182 . https://doi.org/10.1038/s41580-020-0272-6 https://doi.org/10.1038/s41580-020-0272-6

Lawrimore J , Kolbin D , Stanton J , et al. , 2021 . The rDNA is biomolecular condensate formed by polymer-polymer phase separation and is sequestered in the nucleolus by transcription and R-loops . Nucleic Acids Res , 49 ( 8 ): 4586 - 4598 . https://doi.org/10.1093/nar/gkab229 https://doi.org/10.1093/nar/gkab229

le Goff S , Boussaid I , Floquet C , et al. , 2021 . p53 activation during ribosome biogenesis regulates normal erythroid differentiation . Blood , 137 ( 1 ): 89 - 102 . https://doi.org/10.1182/blood.2019003439 https://doi.org/10.1182/blood.2019003439

Levasseur J , Nysjö J , Sandy R , et al. , 2018 . Orbital volume and shape in Treacher Collins syndrome . J Cranio-Maxillofac Surg , 46 ( 2 ): 305 - 311 . https://doi.org/10.1016/j.jcms.2017.11.028 https://doi.org/10.1016/j.jcms.2017.11.028

Levine AJ , 2020 . p53: 800 million years of evolution and 40 years of discovery . Nat Rev Cancer , 20 ( 8 ): 471 - 480 . https://doi.org/10.1038/s41568-020-0262-1 https://doi.org/10.1038/s41568-020-0262-1

Li YM , Zhou Y , Li BF , et al. , 2020 . WDR74 modulates melanoma tumorigenesis and metastasis through the RPL5-MDM2-p53 pathway . Oncogene , 39 ( 13 ): 2741 - 2755 . https://doi.org/10.1038/s41388-020-1179-6 https://doi.org/10.1038/s41388-020-1179-6

Liebl MC , Hofmann TG , 2021 . The role of p53 signaling in colorectal cancer . Cancers , 13 ( 9 ): 2125 . https://doi.org/10.3390/cancers13092125 https://doi.org/10.3390/cancers13092125

Liu J , Zhang C , Hu WW , et al. , 2019 . Tumor suppressor p53 and metabolism . J Mol Cell Biol , 11 ( 4 ): 284 - 292 . https://doi.org/10.1093/jmcb/mjy070 https://doi.org/10.1093/jmcb/mjy070

Ljungström V , Cortese D , Young E , et al. , 2016 . Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations . Blood , 127 ( 8 ): 1007 - 1016 . https://doi.org/10.1182/blood-2015-10-674572 https://doi.org/10.1182/blood-2015-10-674572

Lowry RB , Innes AM , Bernier FP , et al. , 2003 . Bowen-Conradi syndrome: a clinical and genetic study . Am J Med Genet A , 120 A( 3 ): 423 - 428 . https://doi.org/10.1002/ajmg.a.20059 https://doi.org/10.1002/ajmg.a.20059

Lyon AS , Peeples WB , Rosen MK , 2021 . A framework for understanding the functions of biomolecular condensates across scales . Nat Rev Mol Cell Biol , 22 ( 3 ): 215 - 235 . https://doi.org/10.1038/s41580-020-00303-z https://doi.org/10.1038/s41580-020-00303-z

Maiser A , Dillinger S , Längst G , et al. , 2020 . Super-resolution in situ analysis of active ribosomal DNA chromatin organization in the nucleolus . Sci Rep , 10 : 7462 . https://doi.org/10.1038/s41598-020-64589-x https://doi.org/10.1038/s41598-020-64589-x

Mäkitie OM , Tapanainen PJ , Dunkel L , et al. , 2001 . Impaired spermatogenesis: an unrecognized feature of cartilage-hair hypoplasia . Ann Med , 33 ( 3 ): 201 - 205 . https://doi.org/10.3109/07853890109002078 https://doi.org/10.3109/07853890109002078

Marcel V , Ghayad SE , Belin S , et al. , 2013 . p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer . Cancer Cell , 24 ( 3 ): 318 - 330 . https://doi.org/10.1016/j.ccr.2013.08.013 https://doi.org/10.1016/j.ccr.2013.08.013

Marszałek-Kruk BA , Wójcicki P , Dowgierd K , et al. , 2021 . Treacher Collins syndrome: genetics, clinical features and management . Genes , 12 ( 9 ): 1392 . https://doi.org/10.3390/genes12091392 https://doi.org/10.3390/genes12091392

Matesic D , Hagan JB , 2007 . Cartilage-hair hypoplasia . Mayo Clin Proc , 82 ( 6 ): 655 . https://doi.org/10.4065/82.6.655 https://doi.org/10.4065/82.6.655

Matsumori H , Watanabe K , Tachiwana H , et al. , 2022 . Ribosomal protein L5 facilitates rDNA-bundled condensate and nucleolar assembly . Life Sci Alliance , 5 ( 7 ): e202101045 . https://doi.org/10.26508/lsa.202101045 https://doi.org/10.26508/lsa.202101045

Mattijssen S , Welting TJM , Pruijn GJM , 2010 . RNase MRP and disease . WIREs RNA , 1 ( 1 ): 102 - 116 . https://doi.org/10.1002/wrna.9 https://doi.org/10.1002/wrna.9

McGowan KA , Li JZ , Park CY , et al. , 2008 . Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects . Nat Genet , 40 ( 8 ): 963 - 970 . https://doi.org/10.1038/ng.188 https://doi.org/10.1038/ng.188

Mensah MA , Niskanen H , Magalhaes AP , et al. , 2023 . Aberrant phase separation and nucleolar dysfunction in rare genetic diseases . Nature , 614 ( 7948 ): 564 - 571 . https://doi.org/10.1038/s41586-022-05682-1 https://doi.org/10.1038/s41586-022-05682-1

Meyer B , Wurm JP , Kötter P , et al. , 2011 . The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ1191 in yeast 18S rRNA . Nucleic Acids Res , 39 ( 4 ): 1526 - 1537 . https://doi.org/10.1093/nar/gkq931 https://doi.org/10.1093/nar/gkq931

Mills EW , Green R , 2017 . Ribosomopathies: there’s strength in numbers . Science , 358 ( 6363 ): eaan2755 . https://doi.org/10.1126/science.aan2755 https://doi.org/10.1126/science.aan2755

Mirabello L , Macari ER , Jessop L , et al. , 2014 . Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families . Blood , 124 ( 1 ): 24 - 32 . https://doi.org/10.1182/blood-2013-11-540278 https://doi.org/10.1182/blood-2013-11-540278

Mirabello L , Khincha PP , Ellis SR , et al. , 2017 . Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation . J Med Genet , 54 ( 6 ): 417 - 425 . https://doi.org/10.1136/jmedgenet-2016-104346 https://doi.org/10.1136/jmedgenet-2016-104346

Mitrea DM , Cika JA , Guy CS , et al. , 2016 . Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA . eLife , 5 : e13571 . https://doi.org/10.7554/eLife.13571 https://doi.org/10.7554/eLife.13571

Morimoto K , Lin S , Sakamoto K , 2007 . The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a review . Mol Genet Metab , 90 ( 4 ): 358 - 362 . https://doi.org/10.1016/j.ymgme.2006.11.004 https://doi.org/10.1016/j.ymgme.2006.11.004

Moss T , Mars JC , Tremblay MG , et al. , 2019 . The chromatin landscape of the ribosomal RNA genes in mouse and human . Chromosome Res , 27 ( 1-2 ): 31 - 40 . https://doi.org/10.1007/s10577-018-09603-9 https://doi.org/10.1007/s10577-018-09603-9

Nachmani D , Bothmer AH , Grisendi S , et al. , 2019 . Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita . Nat Genet , 51 ( 10 ): 1518 - 1529 . https://doi.org/10.1038/s41588-019-0502-z https://doi.org/10.1038/s41588-019-0502-z

Narla A , Ebert BL , 2010 . Ribosomopathies: human disorders of ribosome dysfunction . Blood , 115 ( 16 ): 3196 - 3205 . https://doi.org/10.1182/blood-2009-10-178129 https://doi.org/10.1182/blood-2009-10-178129

Nelson JO , Watase GJ , Warsinger-Pepe N , et al. , 2019 . Mechanisms of rDNA copy number maintenance . Trends Genet , 35 ( 10 ): 734 - 742 . https://doi.org/10.1016/j.tig.2019.07.006 https://doi.org/10.1016/j.tig.2019.07.006

Nerurkar P , Altvater M , Gerhardy S , et al. , 2015 . Eukaryotic ribosome assembly and nuclear export . Int Rev Cell Mol Biol , 319 : 107 - 140 . https://doi.org/10.1016/bs.ircmb.2015.07.002 https://doi.org/10.1016/bs.ircmb.2015.07.002

Nieminen TT , O'Donohue MF , Wu YP , et al. , 2014 . Germline mutation of RPS20 , encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency . Gastroenterology , 147 ( 3 ): 595 - 598.e5 . https://doi.org/10.1053/j.gastro.2014.06.009 https://doi.org/10.1053/j.gastro.2014.06.009

Noack Watt KE , Achilleos A , Neben CL , et al. , 2016 . The roles of RNA polymerase I and III subunits polr1c and polr1d in craniofacial development and in zebrafish models of Treacher Collins syndrome . PLoS Genet , 12 ( 7 ): e1006187 . https://doi.org/10.1371/journal.pgen.1006187 https://doi.org/10.1371/journal.pgen.1006187

Noda NN , Wang Z , Zhang H , 2020 . Liquid-liquid phase separation in autophagy . J Cell Biol , 219 ( 8 ): e202004062 . https://doi.org/10.1083/jcb.202004062 https://doi.org/10.1083/jcb.202004062

Norris K , Hopes T , Aspden JL , 2021 . Ribosome heterogeneity and specialization in development . WIREs RNA , 12 ( 4 ): e1644 . https://doi.org/10.1002/wrna.1644 https://doi.org/10.1002/wrna.1644

Nott TJ , Craggs TD , Baldwin AJ , 2016 . Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters . Nat Chem , 8 ( 6 ): 569 - 575 . https://doi.org/10.1038/nchem.2519 https://doi.org/10.1038/nchem.2519

Ohashi R , Umezu H , Sato A , et al. , 2020 . Frequent germline and somatic single nucleotide variants in the promoter region of the ribosomal RNA gene in Japanese lung adenocarcinoma patients . Cells , 9 ( 11 ): 2409 . https://doi.org/10.3390/cells9112409 https://doi.org/10.3390/cells9112409

Ojha S , Malla S , Lyons SM , 2020 . SnoRNPs: functions in ribosome biogenesis . Biomolecules , 10 ( 5 ): 783 . https://doi.org/10.3390/biom10050783 https://doi.org/10.3390/biom10050783

Ong JY , Torres JZ , 2020 . Phase separation in cell division . Mol Cell , 80 ( 1 ): 9 - 20 . https://doi.org/10.1016/j.molcel.2020.08.007 https://doi.org/10.1016/j.molcel.2020.08.007

Orelio C , Verkuijlen P , Geissler J , et al. , 2009 . SBDS expression and localization at the mitotic spindle in human myeloid progenitors . PLoS ONE , 4 ( 9 ): e7084 . https://doi.org/10.1371/journal.pone.0007084 https://doi.org/10.1371/journal.pone.0007084

Panda A , Yadav A , Yeerna H , et al. , 2020 . Tissue- and development-stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples . Nucleic Acids Res , 48 ( 13 ): 7079 - 7098 . https://doi.org/10.1093/nar/gkaa485 https://doi.org/10.1093/nar/gkaa485

Panić L , Tamarut S , Sticker-Jantscheff M , et al. , 2006 . Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation . Mol Cell Biol , 26 ( 23 ): 8880 - 8891 . https://doi.org/10.1128/MCB.00751-06 https://doi.org/10.1128/MCB.00751-06

Paolini NA , Attwood M , Sondalle SB , et al. , 2017 . A ribosomopathy reveals decoding defective ribosomes driving human dysmorphism . Am J Hum Genet , 100 ( 3 ): 506 - 522 . https://doi.org/10.1016/j.ajhg.2017.01.034 https://doi.org/10.1016/j.ajhg.2017.01.034

Pederson T , 2011 . The nucleolus . Cold Spring Harb Perspect Biol , 3 ( 3 ): a000638 . https://doi.org/10.1101/cshperspect.a000638 https://doi.org/10.1101/cshperspect.a000638

Peña C , Hurt E , Panse VG , 2017 . Eukaryotic ribosome assembly, transport and quality control . Nat Struct Mol Biol , 24 ( 9 ): 689 - 699 . https://doi.org/10.1038/nsmb.3454 https://doi.org/10.1038/nsmb.3454

Pfister AS , 2019 . Emerging role of the nucleolar stress response in autophagy . Front Cell Neurosci , 13 : 156 . https://doi.org/10.3389/fncel.2019.00156 https://doi.org/10.3389/fncel.2019.00156

Pilla SP , Bahadur RP , 2019 . Residue conservation elucidates the evolution of r-proteins in ribosomal assembly and function . Int J Biol Macromol , 140 : 323 - 329 . https://doi.org/10.1016/j.ijbiomac.2019.08.127 https://doi.org/10.1016/j.ijbiomac.2019.08.127

Plomp RG , van Lieshout MJS , Joosten KFM , et al. , 2016 . Treacher Collins syndrome: a systematic review of evidence-based treatment and recommendations . Plast Reconstr Surg , 137 ( 1 ): 191 - 204 . https://doi.org/10.1097/PRS.0000000000001896 https://doi.org/10.1097/PRS.0000000000001896

Provost E , Wehner KA , Zhong XG , et al. , 2012 . Ribosomal biogenesis genes play an essential and p53-independent role in zebrafish pancreas development . Development , 139 ( 17 ): 3232 - 3241 . https://doi.org/10.1242/dev.077107 https://doi.org/10.1242/dev.077107

Pyo AGT , Zhang YJ , Wingreen NS , 2022 . Surface tension and super-stoichiometric surface enrichment in two-component biomolecular condensates . iScience , 25 ( 2 ): 103852 . https://doi.org/10.1016/j.isci.2022.103852 https://doi.org/10.1016/j.isci.2022.103852

Rabl J , Leibundgut M , Ataide SF , et al. , 2011 . Crystal structure of the eukaryotic 40 S ribosomal subunit in complex with initiation factor 1 . Science , 331 ( 6018 ): 730 - 736 . https://doi.org/10.1126/science.1198308 https://doi.org/10.1126/science.1198308

Rieder D , Trajanoski Z , McNally JG , 2012 . Transcription factories . Front Genet , 3 : 221 . https://doi.org/10.3389/fgene.2012.00221 https://doi.org/10.3389/fgene.2012.00221

Robertson N , Shchepachev V , Wright D , et al. , 2022 . A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis . Nat Commun , 13 : 649 . https://doi.org/10.1038/s41467-022-28295-8 https://doi.org/10.1038/s41467-022-28295-8

Sakai D , Trainor PA , 2009 . Treacher Collins syndrome: unmasking the role of Tcof1 /treacle . Int J Biochem Cell Biol , 41 ( 6 ): 1229 - 1232 . https://doi.org/10.1016/j.biocel.2008.10.026 https://doi.org/10.1016/j.biocel.2008.10.026

Sanchez E , Laplace-Builhé B , Mau-Them FT , et al. , 2020 . POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4 . Genet Med , 22 ( 3 ): 547 - 556 . https://doi.org/10.1038/s41436-019-0669-9 https://doi.org/10.1038/s41436-019-0669-9

Schreiner C , Kernl B , Dietmann P , et al. , 2022 . The ribosomal protein L5 functions during Xenopus anterior development through apoptotic pathways . Front Cell Dev Biol , 10 : 777121 . https://doi.org/10.3389/fcell.2022.777121 https://doi.org/10.3389/fcell.2022.777121

Shi Z , Fujii K , Kovary KM , et al. , 2017 . Heterogeneous ribosomes preferentially translate distinct subpools of mRNAs genome-wide . Mol Cell , 67 ( 1 ): 71 - 83.e7 . https://doi.org/10.1016/j.molcel.2017.05.021 https://doi.org/10.1016/j.molcel.2017.05.021

Shigeoka T , Koppers M , Wong HHW , et al. , 2019 . On-site ribosome remodeling by locally synthesized ribosomal proteins in axons . Cell Rep , 29 ( 11 ): 3605 - 3619.e10 . https://doi.org/10.1016/j.celrep.2019.11.025 https://doi.org/10.1016/j.celrep.2019.11.025

Shin Y , Brangwynne CP , 2017 . Liquid phase condensation in cell physiology and disease . Science , 357 ( 6357 ): eaaf4382 . https://doi.org/10.1126/science.aaf4382 https://doi.org/10.1126/science.aaf4382

Shin Y , Chang YC , Lee DSW , et al. , 2018 . Liquid nuclear condensates mechanically sense and restructure the genome . Cell , 175 ( 6 ): 1481 - 1491.e13 . https://doi.org/10.1016/j.cell.2018.10.057 https://doi.org/10.1016/j.cell.2018.10.057

Shubina MY , Arifulin EA , Sorokin DV , et al. , 2020 . The GAR domain integrates functions that are necessary for the proper localization of fibrillarin (FBL) inside eukaryotic cells . PeerJ , 8 : e9029 . https://doi.org/10.7717/peerj.9029 https://doi.org/10.7717/peerj.9029

Slavov N , Semrau S , Airoldi E , et al. , 2015 . Differential stoichiometry among core ribosomal proteins . Cell Rep , 13 ( 5 ): 865 - 873 . https://doi.org/10.1016/j.celrep.2015.09.056 https://doi.org/10.1016/j.celrep.2015.09.056

Sloan KE , Warda AS , Sharma S , et al. , 2017 . Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function . RNA Biol , 14 ( 9 ): 1138 - 1152 . https://doi.org/10.1080/15476286.2016.1259781 https://doi.org/10.1080/15476286.2016.1259781

Smallwood K , Watt KEN , Ide S , et al. , 2023 . POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies . Am J Hum Genet , 110 ( 5 ): 809 - 825 . https://doi.org/10.1016/j.ajhg.2023.03.014 https://doi.org/10.1016/j.ajhg.2023.03.014

Smirnov E , Hornáček M , Kováčik L , et al. , 2016 . Reproduction of the FC/DFC units in nucleoli . Nucleus , 7 ( 2 ): 203 - 215 . https://doi.org/10.1080/19491034.2016.1157674 https://doi.org/10.1080/19491034.2016.1157674

Sondalle SB , Baserga SJ , 2014 . Human diseases of the SSU processome . Biochim Biophys Acta , 1842 ( 6 ): 758 - 764 . https://doi.org/10.1016/j.bbadis.2013.11.004 https://doi.org/10.1016/j.bbadis.2013.11.004

Spannl S , Tereshchenko M , Mastromarco GJ , et al. , 2019 . Biomolecular condensates in neurodegeneration and cancer . Traffic , 20 ( 12 ): 890 - 911 . https://doi.org/10.1111/tra.12704 https://doi.org/10.1111/tra.12704

Strickfaden H , Tolsma TO , Sharma A , et al. , 2020 . Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells . Cell , 183 ( 7 ): 1772 - 1784.e13 . https://doi.org/10.1016/j.cell.2020.11.027 https://doi.org/10.1016/j.cell.2020.11.027

Su Q , Mehta S , Zhang J , 2021 . Liquid-liquid phase separation: orchestrating cell signaling through time and space . Mol Cell , 81 ( 20 ): 4137 - 4146 . https://doi.org/10.1016/j.molcel.2021.09.010 https://doi.org/10.1016/j.molcel.2021.09.010

Taoka M , Nobe Y , Yamaki Y , et al. , 2018 . Landscape of the complete RNA chemical modifications in the human 80S ribosome . Nucleic Acids Res , 46 ( 18 ): 9289 - 9298 . https://doi.org/10.1093/nar/gky811 https://doi.org/10.1093/nar/gky811

Terrazas K , Dixon J , Trainor PA , et al. , 2017 . Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses . WIREs Dev Biol , 6 ( 3 ): e263 . https://doi.org/10.1002/wdev.263 https://doi.org/10.1002/wdev.263

Thiel CT , Mortier G , Kaitila I , et al. , 2007 . Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum . Am J Hum Genet , 81 ( 3 ): 519 - 529 . https://doi.org/10.1086/521034 https://doi.org/10.1086/521034

Thomas SR , Keller CA , Szyk A , et al. , 2011 . Structural insight into the functional mechanism of Nep1/Emg1 N1-specific pseudouridine methyltransferase in ribosome biogenesis . Nucleic Acids Res , 39 ( 6 ): 2445 - 2457 . https://doi.org/10.1093/nar/gkq1131 https://doi.org/10.1093/nar/gkq1131

Tong DD , Zhang J , Wang XF , et al. , 2020 . MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription . Oncogenesis , 9 : 56 . https://doi.org/10.1038/s41389-020-0239-7 https://doi.org/10.1038/s41389-020-0239-7

Tourlakis ME , Zhang SY , Ball HL , et al. , 2015 . In vivo senescence in the Sbds-deficient murine pancreas: cell-type specific consequences of translation insufficiency . PLoS Genet , 11 ( 6 ): e1005288 . https://doi.org/10.1371/journal.pgen.1005288 https://doi.org/10.1371/journal.pgen.1005288

Tsang B , Pritišanac I , Scherer SW , et al. , 2020 . Phase separation as a missing mechanism for interpretation of disease mutations . Cell , 183 ( 7 ): 1742 - 1756 . https://doi.org/10.1016/j.cell.2020.11.050 https://doi.org/10.1016/j.cell.2020.11.050

Tse WKF , 2016 . Treacher Collins syndrome: new insights from animal models . Int J Biochem Cell Biol , 81 : 44 - 47 . https://doi.org/10.1016/j.biocel.2016.10.016 https://doi.org/10.1016/j.biocel.2016.10.016

Tsekrekou M , Stratigi K , Chatzinikolaou G , 2017 . The nucleolus: in genome maintenance and repair . Int J Mol Sci , 18 ( 7 ): 1411 . https://doi.org/10.3390/ijms18071411 https://doi.org/10.3390/ijms18071411

Turi Z , Senkyrikova M , Mistrik M , et al. , 2018 . Perturbation of RNA polymerase I transcription machinery by ablation of HEATR1 triggers the RPL5/RPL11-MDM2-p53 ribosome biogenesis stress checkpoint pathway in human cells . Cell Cycle , 17 ( 1 ): 92 - 101 . https://doi.org/10.1080/15384101.2017.1403685 https://doi.org/10.1080/15384101.2017.1403685

Uversky VN , 2017 . Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder . Curr Opin Struct Biol , 44 : 18 - 30 . https://doi.org/10.1016/j.sbi.2016.10.015 https://doi.org/10.1016/j.sbi.2016.10.015

Vakkilainen S , Taskinen M , Mäkitie O , 2020 . Immunodeficiency in cartilage-hair hypoplasia: pathogenesis, clinical course and management . Scand J Immunol , 92 ( 4 ): e12913 . https://doi.org/10.1111/sji.12913 https://doi.org/10.1111/sji.12913

van Sluis M , McStay B , 2017 . Nucleolar reorganization in response to rDNA damage . Curr Opin Cell Biol , 46 : 81 - 86 . https://doi.org/10.1016/j.ceb.2017.03.004 https://doi.org/10.1016/j.ceb.2017.03.004

Venturi G , Montanaro L , 2020 . How altered ribosome production can cause or contribute to human disease: the spectrum of ribosomopathies . Cells , 9 ( 10 ): 2300 . https://doi.org/10.3390/cells9102300 https://doi.org/10.3390/cells9102300

Vulliamy T , Beswick R , Kirwan M , et al. , 2008 . Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita . Proc Natl Acad Sci USA , 105 ( 23 ): 8073 - 8078 . https://doi.org/10.1073/pnas.0800042105 https://doi.org/10.1073/pnas.0800042105

Vulliamy TJ , Dokal I , 2008 . Dyskeratosis congenita: the diverse clinical presentation of mutations in the telomerase complex . Biochimie , 90 ( 1 ): 122 - 130 . https://doi.org/10.1016/j.biochi.2007.07.017 https://doi.org/10.1016/j.biochi.2007.07.017

Wang B , Zhang L , Dai T , et al. , 2021 . Liquid‒liquid phase separation in human health and diseases . Signal Transduct Target Ther , 6 : 290 . https://doi.org/10.1038/s41392-021-00678-1 https://doi.org/10.1038/s41392-021-00678-1

Wang M , Lemos B , 2017 . Ribosomal DNA copy number amplification and loss in human cancers is linked to tumor genetic context, nucleolus activity, and proliferation . PLoS Genet , 13 ( 9 ): e1006994 . https://doi.org/10.1371/journal.pgen.1006994 https://doi.org/10.1371/journal.pgen.1006994

Warda AS , Freytag B , Haag S , et al. , 2016 . Effects of the Bowen-Conradi syndrome mutation in EMG1 on its nuclear import, stability and nucleolar recruitment . Hum Mol Genet , 25 ( 24 ): 5353 - 5364 . https://doi.org/10.1093/hmg/ddw351 https://doi.org/10.1093/hmg/ddw351

Warren AJ , 2018 . Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome . Adv Biol Regul , 67 : 109 - 127 . https://doi.org/10.1016/j.jbior.2017.09.002 https://doi.org/10.1016/j.jbior.2017.09.002

Watt KEN , Neben CL , Hall S , et al. , 2018 . tp53 -dependent and independent signaling underlies the pathogenesis and possible prevention of Acrofacial Dysostosis-Cincinnati type . Hum Mol Genet , 27 ( 15 ): 2628 - 2643 . https://doi.org/10.1093/hmg/ddy172 https://doi.org/10.1093/hmg/ddy172

Weis F , Giudice E , Churcher M , et al. , 2015 . Mechanism of eIF6 release from the nascent 60S ribosomal subunit . Nat Struct Mol Biol , 22 ( 11 ): 914 - 919 . https://doi.org/10.1038/nsmb.3112 https://doi.org/10.1038/nsmb.3112

Welsh TJ , Shen Y , Levin A , et al. , 2018 . Mechanobiology of protein droplets: force arises from disorder . Cell , 175 ( 6 ): 1457 - 1459 . https://doi.org/10.1016/j.cell.2018.11.020 https://doi.org/10.1016/j.cell.2018.11.020

Wilson DN , Doudna Cate JH , 2012 . The structure and function of the eukaryotic ribosome . Cold Spring Harb Perspect Biol , 4 ( 5 ): a011536 . https://doi.org/10.1101/cshperspect.a011536 https://doi.org/10.1101/cshperspect.a011536

Wlodarski MW , da Costa L , O'Donohue MF , et al. , 2018 . Recurring mutations in RPL15 are linked to hydrops fetalis and treatment independence in Diamond-Blackfan anemia . Haematologica , 103 ( 6 ): 949 - 958 . https://doi.org/10.3324/haematol.2017.177980 https://doi.org/10.3324/haematol.2017.177980

Wu DY , Prives C , 2018 . Relevance of the p53‒MDM2 axis to aging . Cell Death Differ , 25 ( 1 ): 169 - 179 . https://doi.org/10.1038/cdd.2017.187 https://doi.org/10.1038/cdd.2017.187

Wu M , Xu G , Han C , et al. , 2021 . lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription . Science , 373 ( 6554 ): 547 - 555 . https://doi.org/10.1126/science.abf6582 https://doi.org/10.1126/science.abf6582

Wurm JP , Meyer B , Bahr U , et al. , 2010 . The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase . Nucleic Acids Res , 38 ( 7 ): 2387 - 2398 . https://doi.org/10.1093/nar/gkp1189 https://doi.org/10.1093/nar/gkp1189

Xia J , Miller CA , Baty J , et al. , 2018 . Somatic mutations and clonal hematopoiesis in congenital neutropenia . Blood , 131 ( 4 ): 408 - 416 . https://doi.org/10.1182/blood-2017-08-801985 https://doi.org/10.1182/blood-2017-08-801985

Xu BS , Li H , Perry JM , et al. , 2017 . Ribosomal DNA copy number loss and sequence variation in cancer . PLoS Genet , 13 ( 6 ): e1006771 . https://doi.org/10.1371/journal.pgen.1006771 https://doi.org/10.1371/journal.pgen.1006771

Xue SF , Barna M , 2012 . Specialized ribosomes: a new frontier in gene regulation and organismal biology . Nat Rev Mol Cell Biol , 13 ( 6 ): 355 - 369 . https://doi.org/10.1038/nrm3359 https://doi.org/10.1038/nrm3359

Xue SF , Tian SQ , Fujii K , et al. , 2015 . RNA regulons in Hox 5' UTRs confer ribosome specificity to gene regulation . Nature , 517 ( 7532 ): 33 - 38 . https://doi.org/10.1038/nature14010 https://doi.org/10.1038/nature14010

Yao RW , Xu G , Wang Y , et al. , 2019 . Nascent pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus . Mol Cell , 76 ( 5 ): 767 - 783.e11 . https://doi.org/10.1016/j.molcel.2019.08.014 https://doi.org/10.1016/j.molcel.2019.08.014

Yu L , Lemay P , Ludlow A , et al. , 2021 . A new murine Rpl5 ( uL18 ) mutation provides a unique model of variably penetrant Diamond-Blackfan anemia . Blood Adv , 5 ( 20 ): 4167 - 4178 . https://doi.org/10.1182/bloodadvances.2021004658 https://doi.org/10.1182/bloodadvances.2021004658

Zeng ML , Shang Y , Araki Y , et al. , 2016 . Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity . Cell , 166 ( 5 ): 1163 - 1175.e12 . https://doi.org/10.1016/j.cell.2016.07.008 https://doi.org/10.1016/j.cell.2016.07.008

Zhang H , Ji X , Li PL , et al. , 2020 . Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases . Sci China Life Sci , 63 ( 7 ): 953 - 985 . https://doi.org/10.1007/s11427-020-1702-x https://doi.org/10.1007/s11427-020-1702-x

Zhao CT , Andreeva V , Gibert Y , et al. , 2014 . Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development . PLoS Genet , 10 ( 1 ): e1004074 . https://doi.org/10.1371/journal.pgen.1004074 https://doi.org/10.1371/journal.pgen.1004074

Zhao YG , Zhang H , 2020 . Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates . Dev Cell , 55 ( 1 ): 30 - 44 . https://doi.org/10.1016/j.devcel.2020.06.033 https://doi.org/10.1016/j.devcel.2020.06.033

Zhou X , Liao WJ , Liao JM , et al. , 2015a . Ribosomal proteins: functions beyond the ribosome . J Mol Cell Biol , 7 ( 2 ): 92 - 104 . https://doi.org/10.1093/jmcb/mjv014 https://doi.org/10.1093/jmcb/mjv014

Zhou X , Hao Q , Zhang Q , et al. , 2015b . Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition . Cell Death Differ , 22 ( 5 ): 755 - 766 . https://doi.org/10.1038/cdd.2014.167 https://doi.org/10.1038/cdd.2014.167

Zhu YQ , Wang Y , Tao BX , et al. , 2022 . Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication . J Mol Cell Biol , 13 ( 12 ): 902 - 917 . https://doi.org/10.1093/jmcb/mjab074 https://doi.org/10.1093/jmcb/mjab074

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