Ribosome heterogeneity and specialization

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2025, Номер 380(1921)

Опубликована: Март 6, 2025

Open AccessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations Share ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Aspden Julie, Faller William James, Barna Maria and Lund Anders 2025Ribosome heterogeneity specializationPhil. Trans. R. Soc. B38020230375http://doi.org/10.1098/rstb.2023.0375SectionOpen AccessIntroductionRibosome specialization Julie https://orcid.org/0000-0002-8537-6204 School of Molecular Cellular Biology, Faculty Biological Sciences, University Leeds, Leeds LS2 9JT, UK LeedsOmics, Astbury Centre for Structural [email protected] Contribution: Writing – original draft, review editing Google Scholar Find author on PubMed Search more papers by , James https://orcid.org/0000-0002-0738-2254 Netherlands Cancer Institute, Amsterdam, The Stanford University, Stanford, CA, USA Biotech Research Innovation Centre, Copenhagen, Kobenhavn DK-2200, Denmark Published:06 March 2025https://doi.org/10.1098/rstb.2023.03751. Historical perspectiveThe historical journey ribosome research has undergone significant shifts, evolving from an initial perception ribosomes as uniform molecular machines their current recognition dynamic regulators translation. In the mid-1950s, George Palade, using electron microscopy, first described small particulate structures in cytoplasm, which he initially termed 'microsomes' [1]. These were later identified sites protein synthesis, term 'ribosome' was officially coined at a 1958 Biophysical Society symposium. Shortly after discovery, notion introduced Francis Crick his 'one gene–one ribosome–one protein' hypothesis [2], proposed that each specialized synthesize single protein. However, quickly challenged early 1960s experiments Sydney Brenner, François Jacob Matthew Meselson, whose facilitated are non-specialized different proteins depending mRNA they contain [3]. findings led prevailing dogma function passive, homogeneous entities translation, perspective dominated biology decades.Despite dismissal, sporadic observations emerged throughout late twentieth century [4]. Studies 1980s 1990s tissue-specific ribosomal (RP) paralogue expression plants invertebrates, well variation RNA (rRNA) sequences Plasmodium [5] during life cycle stages. turn century, researchers discovered certain RPs essential specific developmental processes Drosophila [6] vertebrates [7], leading distinct phenotypic effects rather than global translation defects (reviewed [8]). By 2000s, advances techniques, including profiling quantitative mass spectrometry, began revealing direct evidence specialization. For instance, studies demonstrated actively translating mouse embryonic stem cells exhibited compositional diversity [9], with influencing subsets mRNAs [10]. Ribosome now extends stress states bacteria [11] yeast [12,13], neurons [14], germ line [15,16], development [17,18] immunity [19],to name few.Thereby, story is not just one scientific discovery but also shifting paradigms how we understand biological complexity. At its core, it reflection broader philosophical tension biology: struggle between reductionism emergent view aligned reductionist framework mid-twentieth biology—a time when central gene being solidified. model, merely passive conduit genetic information, faithfully into without bias or This offered comforting simplicity, reducing complexity set uniform, predictable biochemical processes. history shown again, nature resists oversimplification. emerging challenges mechanistic view, forcing shift toward dynamic, systems-level understanding regulation. further favours that, whenever evolution you can regulate, do, achieve greater life.In many ways, embodies concept plasticity—its form fixed instead adapt physiological needs organism. mirrors theme identity static context-dependent, principle seen cell differentiation, neural plasticity even ecological adaptation. specialized, selectively translate tissues stages, suggests governed universal rules sculpted intricate regulatory networks respond moves us away deterministic idea genes alone dictate outcomes, holistic cell, tissue contribute final potential. specialization, then, mechanism—it life's ability fine-tune itself, carve out specificity meaning what once thought be universal. reflected fact today's exploring composition influences regulation, cellular differentiation disease states, positioning fundamental mechanism our know it.2. Royal meetingIn November 2023, Hooke Discussion Meeting brought together international scientists share perspectives novel insights meeting discussed latest advances, covering all types variety organisms systems, impact human disease. organized Dr Aspden, Barna, H. Lund. Contributions came numerous disciplines, such structural biology, cancer biochemistry, neuroscience. Talks posters focused range heterogeneity, switching events, rRNA modification changes cancer, association modulatory core ribosome.Importantly, community attempting unravel functional implications wide systems approaches. results come melanogaster, Danio rerio, intestinal cells, viral infection, plants. study examples species will widespread similar translational impacts achieved through composition. A good example ways peptide exit channel modified enable regulation nascent folding elongation dynamics [16].Talks covered biogenesis heterogeneous ribosomes, stimulates (e.g. stresses), affect structure ribosome, these organism, phenotypes.3. Technical advancesA common among talks technology driving field forward. As young fields, there have been teething problems technologies used identify analyse ribosomes. nature, difficult study, sequencing, proteomic visualization techniques presented problems. developed, adapted purpose toolbox available growing steadily.Adaptations high-throughput approaches proven particularly fruitful. While sequencing over decade modifications [20,21], long-read associated analysis tools, provided new window [22,23]. Similar allow transcript variation. high number homology rDNA previously prevented reliable transcripts, something overcome [24].Approaches complement handle difficulties studying ribosome-associated (RAPs). coming years, expansion microscopy should vivo populations, although yet happen. recently targeted RNase H-mediated extraction cross(X)-linked binding (TREX) methodology provides improved means directly [25], while both RAP identification affinity sulfhydryl-charged resin (RAPIDASH) [26] purification poly-lysine (RAPPL) [27] describe improvements isolation proteins. RAPPL-isolated visualized resolution cryogenic (cryoEM), itself recent [28–31]. Specialized only limited times along those tomography (cryoET) [32], highlight potential shape biology.4. Outstanding questionsWhile important conceptual technological field, questions remain unanswered.First, generated arrays controlled cell? extension, regulated normal processes, hijacked diseases?Second, whereas heterologous populations branches life, characterize subtypes potentially modalities? Here, molecule patterns could stepping stone [33]. Evidently, tagging methods need developed puzzle.Third, several 'translation factories', unique locations where synthesized [34], currently known factories generated, and—importantly—how transported ribosomes.Fourth, given evolutionary conservation see additional functions linked synthesis [35]?Finally, tumour types, altered—presumably facilitate elevated deviant patterns. If 'oncoribosomes' specifically targeted, curtail cancers 'addiction' synthesis.This special issue contains articles, reviews key themes (November 2023). Several discuss employing cutting-edge look future field. We hope enjoy collection articles issue.EthicsThis work did require ethical approval subject animal welfare committee.Data accessibilityThis no data.Declaration AI useWe AI-assisted creating article.Authors' contributionsJ.A.: writing—original writing—review editing; W.J.F.: M.B.: A.L.: editing.All authors gave publication agreed held accountable performed herein.Conflict interest declarationThis put Guest Editor team under supervision journal's Editorial staff, following Society's codes best-practice guidelines. invited contributions handled process. Individual Editors involved assessing had personal, professional financial conflict described. Independent reviewers assessed papers. Invitation guarantee inclusion.FundingNo funding received article.FootnotesOne contribution 14 discussion 'Ribosome disease'.© 2025 Author(s).Published terms Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, permits unrestricted use, source credited. Next Article VIEW FULL TEXTDOWNLOAD FiguresRelatedReferencesDetails Issue06 2025Volume 380Issue 1921Discussion issue'Ribosome disease'organised edited L. J. Faller, InformationDOI:https://doi.org/10.1098/rstb.2023.0375PubMed:40045789Published by:Royal SocietyPrint ISSN:0962-8436Online ISSN:1471-2970History: Manuscript received13/02/2025Manuscript accepted13/02/2025Published online06/03/2025 License:© KeywordsmRNA translationribosomal proteinsprotein synthesisribosomerRNA Subjectscellular biologymolecular biologystructural

Язык: Английский

RNA modifications in the tumor microenvironment: insights into the cancer-immunity cycle and beyond

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Опубликована: Апрель 2, 2025

Язык: Английский