Philosophical Transactions of the Royal Society B: Biological Sciences最新文献

{"title":"High-throughput approaches for the identification of ribosome heterogeneity.","authors":"Edwin S Kyei-Baffour, Qi Chang Lin, Ferhat Alkan, William J Faller","doi":"10.1098/rstb.2023.0381","DOIUrl":"10.1098/rstb.2023.0381","url":null,"abstract":"<p><p>Recent advances in the fields of RNA translation and ribosome biology have demonstrated the heterogeneous nature of ribosomes. This manifests not only across different cellular contexts but also within the same cell. Such variations in ribosomal composition, be it in ribosomal RNAs or proteins, can significantly influence cellular processes and responses by altering the mRNAs being translated or the dynamics of ribosomes during the translation process. Therefore, identifying this heterogeneity is crucial for unravelling the complexity of gene expression across different fields of biology. Here we provide an overview of recent advances in high-throughput techniques for identifying ribosomal heterogeneity. We cover methodologies for probing both rRNA and protein components of the ribosome and encompass the most recent next-generation sequencing and computational analyses, as well as a diverse array of mass spectrometry techniques.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230381"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of ribosomal RNA sequence variation on gene expression and phenotype.","authors":"Griffin A Welfer, Ryan A Brady, S Kundhavai Natchiar, Zoe L Watson, Emily J Rundlet, Jose L Alejo, Anand P Singh, Nitish K Mishra, Roger B Altman, Scott C Blanchard","doi":"10.1098/rstb.2023.0379","DOIUrl":"10.1098/rstb.2023.0379","url":null,"abstract":"<p><p>Since the framing of the Central Dogma, it has been speculated that physically distinct ribosomes within cells may influence gene expression and cellular physiology. While heterogeneity in ribosome composition has been reported in bacteria, protozoans, fungi, zebrafish, mice and humans, its functional implications remain actively debated. Here, we review recent evidence demonstrating that expression of conserved variant ribosomal DNA (rDNA) alleles in bacteria, mice and humans renders their actively translating ribosome pool intrinsically heterogeneous at the level of ribosomal RNA (rRNA). In this context, we discuss reports that nutrient limitation-induced stress in <i>Escherichia coli</i> leads to changes in variant rRNA allele expression, programmatically altering transcription and cellular phenotype. We highlight that cells expressing ribosomes from distinct operons exhibit distinct drug sensitivities, which can be recapitulated <i>in vitro</i> and potentially rationalized by subtle perturbations in ribosome structure or in their dynamic properties. Finally, we discuss evidence that differential expression of variant rDNA alleles results in different populations of ribosome subtypes within mammalian tissues. These findings motivate further research into the impacts of rRNA heterogeneities on ribosomal function and predict that strategies targeting distinct ribosome subtypes may hold therapeutic potential.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230379"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specialized ribosomes: integrating new insights and current challenges.","authors":"Alan J S Beavan, Veronica Thuburn, Bulat Fatkhullin, Joanne Cunningham, Tayah S Hopes, Ella Dimascio, Tessa Chan, Nan Zhao, Karl Norris, Chalmers Chau, Elton J R Vasconcelos, Alison Wood, Adrian Whitehouse, Paolo Actis, Brendan Davies, Juan Fontana, Mary J O'Connell, Emma Thomson, Julie L Aspden","doi":"10.1098/rstb.2023.0377","DOIUrl":"10.1098/rstb.2023.0377","url":null,"abstract":"<p><p>Variation in the composition of different ribosomes, termed ribosome heterogeneity, is a now well established phenomenon. However, the functional implications of this heterogeneity on the regulation of protein synthesis are only now beginning to be revealed. While there are numerous examples of heterogeneous ribosomes, there are comparatively few bona fide specialized ribosomes described. Specialization requires that compositionally distinct ribosomes, through their subtly altered structure, have a functional consequence to the translational output. Even for those examples of ribosome specialization that have been characterized, the precise mechanistic details of how changes in protein and rRNA composition enable the ribosome to regulate translation are still missing. Here, we suggest looking at the evolution of specialization across the tree of life may help reveal central principles of translation regulation. We consider functional and structural studies that have provided insight into the potential mechanisms through which ribosome heterogeneity could affect translation, including through mRNA and open reading frame selectivity, elongation dynamics and post-translational folding. Further, we highlight some of the challenges that must be addressed to show specialization and review the contribution of various models. Several studies are discussed, including recent studies that show how structural insight is starting to shed light on the molecular details of specialization. Finally, we discuss the future of ribosome specialization studies, where advances in technology will likely enable the next wave of research questions. Recent work has helped provide a more comprehensive understanding of how ribosome heterogeneity affects translational control.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230377"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosome-associated proteins: unwRAPping ribosome heterogeneity in the twenty-first century.","authors":"Kitra Cates, Victoria Hung, Maria Barna","doi":"10.1098/rstb.2023.0378","DOIUrl":"10.1098/rstb.2023.0378","url":null,"abstract":"<p><p>The definition of the ribosome as the monolithic machinery in cells that synthesizes all proteins in the cell has persisted for the better part of a century. Yet, research has increasingly revealed that ribosomes are dynamic, multimodal complexes capable of fine-tuning gene expression. This translation regulation may be achieved by ribosome-associated proteins (RAPs), which play key roles as modular trans-acting factors that are dynamic across different cellular contexts and can mediate the recruitment of specific transcripts or the modification of RNA or ribosomal proteins. As a result, RAPs have the potential to rapidly regulate translation within specific subcellular regions, across different cell or tissue types, in response to signalling, or in disease states. In this article, we probe the definition of the eukaryotic ribosome and review the major layers of additional proteins that expand the definition of ribosomes in the twenty-first century. We pose RAPs as key modulators that impart ribosome function in cellular processes, development and disease.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230378"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variant ribosomal DNA is essential for female differentiation in zebrafish.","authors":"Tim V Moser, Donna M Bond, Timothy A Hore","doi":"10.1098/rstb.2024.0107","DOIUrl":"10.1098/rstb.2024.0107","url":null,"abstract":"<p><p>The ribosome consists of protein and RNA components. Deletion of genes encoding specific ribosomal proteins has revealed that heterogeneity in the ribosome must exist in vertebrates; however, this has not been tested for ribosomal RNA (rRNA). In zebrafish (<i>Danio rerio</i>), the '45S-M' ribosomal RNA-encoding locus undergoes massive extrachromosomal amplification during oocyte growth and ovary differentiation and is distinct from the regular ribosomal DNA (rDNA) locus encoding somatic rRNA (45S-S). Although the 45S-M rDNA locus falls within the only described sex-linked region in multiple wild zebrafish strains, its role in sexual differentiation is unclear. We used CRISPR-Cas9 gene editing to alter 45S-M rDNA sequences in zygotes and found that although there was no effect on growth or male development, there was dramatic suppression of female differentiation. Males with edited 45S-M rDNA produced phenotypically normal sperm and were able to fertilize eggs from wild-type females, with resulting embryos once more displaying normal development. Our work supports the hypothesis that specialized 45S-M rDNA is the elusive apical sex-determining locus in zebrafish and that this region represents the most tractable genetic system to date for studying ribosomal RNA heterogeneity and function in a vertebrate.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20240107"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosomal protein paralogues in ribosome specialization.","authors":"Ivan Milenkovic, Eva Maria Novoa","doi":"10.1098/rstb.2023.0387","DOIUrl":"10.1098/rstb.2023.0387","url":null,"abstract":"<p><p>Ribosomes are macromolecular complexes responsible for protein synthesis, comprising ribosomal proteins (RPs) and ribosomal RNA. While most RPs are present as single copies in higher eukaryotes, a handful of them have paralogues that emerged through duplication events. However, it is still unclear why a small subset of RP paralogues were preserved through evolution, and whether they can endow ribosomes with specialized functions. In this review, we focus on RP paralogue pairs present in humans, providing an overview of the most recent findings on RP paralogue functions and their roles in ribosome specialization.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230387"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosomes: from conserved origin to functional/medical mobility and heterogeneity.","authors":"Andre Rivalta, Disha-Gajanan Hiregange, Tanaya Bose, K Shanmugha Rajan, Ada Yonath, Ella Zimmerman, Miriam Waghalter, Gil Fridkin, Irene Martinez-Roman, Liat Rosenfield, Aliza Fedorenko, Anat Bashan, Hagith Yonath","doi":"10.1098/rstb.2023.0393","DOIUrl":"10.1098/rstb.2023.0393","url":null,"abstract":"<p><p>Ribosomes, the molecular machines that translate the genetic code from mRNA into proteins in all living cells, are highly structurally conserved across all domains of life and hence are believed to have evolved from a structurally unified pocket. Initially perceived as uniform cellular factories for protein synthesis, currently, ribosomes have emerged as more complex entities. Structural, medical and biochemical studies, including ours, have revealed significant variability in their compositions across tissues, species, functions and developmental stages, highlighting their multifunctional potential. Moreover, the diversity of ribosomes, their components and their associated biological factors challenge the traditional perception of uniform interactions under various conditions, including stress, and expose their mobility and heterogeneity. Evidence for their functional diversity can be seen even in modifications of ribosomal genes, where minor changes may play critical roles under stress or may lead to diseases called ribosomopathies, including Diamond-Blackfan anaemia, some types of cancer and Alzheimer's disease. Thus, through in-depth structural explorations, we improve the understanding of the mechanisms regulating protein biosynthesis in response to various environmental stressors. These findings should potentially reshape the perceptions of the various ribosomal roles.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230393"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small nucleolar RNAs: the hidden precursors of cancer ribosomes.","authors":"Laurence Faucher-Giguère, Baudouin S de Préval, Andrea Rivera, Michelle S Scott, Sherif Abou Elela","doi":"10.1098/rstb.2023.0376","DOIUrl":"10.1098/rstb.2023.0376","url":null,"abstract":"<p><p>Ribosomes are heterogeneous in terms of their constituent proteins, structural RNAs and ribosomal RNA (rRNA) modifications, resulting in diverse potential translatomes. rRNA modifications, guided by small nucleolar RNAs (snoRNAs), enable fine-tuning of ribosome function and translation profiles. Recent studies have begun linking dysregulation of snoRNAs, via rRNA modifications, to tumourigenesis. Deciphering the specific contributions of individual rRNA modifications to cancer hallmarks and identifying snoRNAs with oncogenic potential could lead to novel therapeutic strategies. These strategies might target snoRNAs or exploit the dependence of cancer cells on specific rRNA modification sites, potentially disrupting aberrant ribosomal translation programs and hindering tumour growth. This review discusses current evidence and challenges in linking changes in snoRNA expression to rRNA modification and cancer biology.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230376"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosomal protein S25 promotes cell cycle entry for a productive BK polyomavirus infection.","authors":"J M Needham, T M Greco, I M Cristea, S R Thompson","doi":"10.1098/rstb.2023.0390","DOIUrl":"10.1098/rstb.2023.0390","url":null,"abstract":"<p><p>Many viruses use alternate mechanisms to initiate protein translation owing to their limited coding capacity. The ribosomal protein S25 (RPS25/eS25) is required for efficient non-canonical mechanisms of translation initiation, such as internal ribosomal entry site (IRES) initiation or ribosomal shunting, but eS25 is not required for efficient cap-dependent initiation. Thus, eS25 knockdown can be used to evaluate whether a virus relies on alternative mechanisms of initiation. Since earlier studies suggest that simian virus 40 (SV40) uses an IRES to translate a minor capsid protein VP3, which is translated from the same transcript as VP2, we sought to test if BK polyomavirus (BKPyV) also used an IRES by examining viral production with and without eS25. Instead, we found that BKPyV required eS25 for robust viral production prior to gene expression, suggesting that it affected an early step in the viral life cycle. These studies revealed a role for eS25 in cell cycle control. When eS25 was knocked down in primary kidney cells, it decreased the proportion of cycling cells, causing arrest at both G0/G1 and G2/M. These data suggest that the timing of BKPyV infection depends on the initial cell cycle state of the host cell.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230390"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building a case for 'functional identity fraud' in eRpL22 paralogue-specific ribosomes in <i>Drosophila</i> germline development.","authors":"Vassie C Ware","doi":"10.1098/rstb.2023.0391","DOIUrl":"10.1098/rstb.2023.0391","url":null,"abstract":"<p><p>Investigations of expression and function of eukaryotic-specific ribosomal protein paralogues, eRpL22 and eRpL22-like, within the <i>Drosophila melanogaster</i> male germline offer valuable insights supporting an emerging paradigm shift that ribosomes are now exempt from the traditional view of being homogeneous protein synthesis machines. Co-expression of these paralogues within the same cell contributes to structural and functional complexity-the latter demonstrated by differential translation specificities based on paralogue content. This commentary highlights some of the key findings related to the biology of specialized ribosomes containing paralogue eRpL22 or eRpL22-like in <i>Drosophila</i> spermatogenesis and raises several unresolved questions about eRpL22 family paralogue function and ribosome-mediated translation regulation within spermatogenesis. Our understanding of principles that govern specialized ribosome function is in nascent stages, and considerably more research is warranted to address the myriad of unresolved questions about specialized ribosomes and the impact on reproductive physiology.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1921","pages":"20230391"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}