{"title":"Single-cell research in Latin America and the Caribbean builds genomics datasets for equitable AI-powered precision medicine.","authors":"Vinicius Maracaja-Coutinho,Helder I Nakaya","doi":"10.1038/s41580-025-00913-5","DOIUrl":"https://doi.org/10.1038/s41580-025-00913-5","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"30 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.","authors":"Carlos Alfonso-Gonzalez,Valérie Hilgers","doi":"10.1038/s41580-025-00895-4","DOIUrl":"https://doi.org/10.1038/s41580-025-00895-4","url":null,"abstract":"The maturation of mRNAs is crucial for gene regulation and proteome diversification. Transcripts are processed co-transcriptionally through a complex interplay of mechanisms that involve numerous protein machineries. In eukaryotes, most genes undergo alternative RNA processing through the context-dependent use of transcription start sites (TSSs), splice sites and polyadenylation sites. The accurate measurement of alternative TSS usage, alternative splicing and alternative polyadenylation has been enabled by short-read RNA-sequencing technologies. However, elucidating the timing, coordination and functional outcomes of alternative RNA processing is challenging, especially in vivo. The development of long-read sequencing (LRS) methodologies enables the characterization of various aspects of co-transcriptional RNA processing, each methodology providing unique perspectives and limitations. In this Review, we discuss recent advances in short-read sequencing and LRS technologies that measure transcripts in their nascent and mature state and at single-cell resolution and with whole-molecule read length in the case of LRS. We integrate new findings that functionally link alternative TSS, alternative splicing and alternative polyadenylation, with new implications for diseases such as cancer and neurodevelopmental and neurodegenerative disorders. Finally, we discuss insights gained using CRISPR tools into the coordination of RNA processing events.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"52 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stem cell sources of colon cancer in mice.","authors":"Kim Baumann","doi":"10.1038/s41580-025-00910-8","DOIUrl":"https://doi.org/10.1038/s41580-025-00910-8","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"54 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.","authors":"Tony Tiganis,Nicholas K Tonks","doi":"10.1038/s41580-025-00882-9","DOIUrl":"https://doi.org/10.1038/s41580-025-00882-9","url":null,"abstract":"Aberrations in protein tyrosine phosphorylation-dependent cell signalling contribute to a wide variety of human diseases. Drugs targeting protein tyrosine kinases have had a major impact on human health; by contrast, protein tyrosine phosphatases (PTPs), which serve unique functions and together with protein tyrosine kinases coordinate tyrosine phosphorylation-dependent cell signalling, have been underexploited therapeutically. In this Review, we discuss key breakthroughs in our understanding of how PTPs are regulated, highlight their capacity to coordinate signalling and provide examples of their complex roles in physiology and pathophysiology, including diabetes, obesity and cancer. Also, we discuss the development of PTP-targeted therapeutics that are in clinical trials or poised for clinical translation. We argue that the emergence of this class of enzymes from the shadows lays the foundation for a more complete understanding of the regulation of cell signalling and heralds a new era of drug development opportunities to combat important human diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"31 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Towards a unified framework for the function of endoplasmic reticulum exit sites.","authors":"Hesso Farhan,Ishier Raote,Felix Campelo,Liang Ge,Koret Hirschberg,Alison Forrester,Giulia Zanetti,Jennifer Lippincott-Schwartz,José Carlos Pastor-Pareja,Franck Perez,Kota Saito,Vivek Malhotra","doi":"10.1038/s41580-025-00899-0","DOIUrl":"https://doi.org/10.1038/s41580-025-00899-0","url":null,"abstract":"Endoplasmic reticulum exit sites (ERES) are specialized, ribosome-free ER subdomains that serve as dynamic portals for COPII-mediated export of proteins from the ER. Beyond their role in the secretory pathway, ERES are implicated in diverse processes, including autophagy and the maturation of lipid droplets, highlighting their functional plasticity. ERES integrate cargo load, membrane tension and spatial cues to remodel their architecture and function in real time. This Roadmap synthesizes our current knowledge on the biogenesis, structural diversity and regulatory logic of ERES. We highlight key unanswered questions in the field, particularly concerning how ERES integrate signals to coordinate protein trafficking under varying cellular states. Finally, we propose a multidisciplinary framework - leveraging advances in high-resolution imaging, synthetic reconstitution and computational modelling - to delineate the principles governing the function and plasticity of ERES. Understanding these mechanisms holds significant potential for developing targeted therapeutic strategies in diseases linked to trafficking dysfunction.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"6 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan N Pruneda,Roko Žaja,Michael S Cohen,Karla L H Feijs-Žaja
{"title":"The emergence of MARUbe - a hybrid ADP-ribose-ubiquitin modification.","authors":"Jonathan N Pruneda,Roko Žaja,Michael S Cohen,Karla L H Feijs-Žaja","doi":"10.1038/s41580-025-00903-7","DOIUrl":"https://doi.org/10.1038/s41580-025-00903-7","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"23 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coordination of cardiogenesis in vivo and in vitro.","authors":"Sasha Mendjan,Alison Deyett,Deborah Yelon","doi":"10.1038/s41580-025-00878-5","DOIUrl":"https://doi.org/10.1038/s41580-025-00878-5","url":null,"abstract":"Heart development has been extensively explored on the anatomical, cellular and molecular levels. Yet, the intricate interplay of tissue organization, cellular lineages and molecular factors that orchestrate heart development, culminating in forming a seamlessly synchronized functional heart, remains challenging to investigate. Mechanistic studies conducted both in vivo using animal models and in vitro stem-cell-derived systems aim to unravel this complexity. In this Review, we discuss how the recent surge in technological advancements in imaging and genomics, coupled with the evolution of next-generation cardiac organoid models, has provided profound insights into these processes, holding significant implications for the development of novel therapies for congenital or acquired heart diseases. We discuss the development of the heart as the first functional organ - from the morphogenesis of the mesoderm, heart tube and cardiac chambers to the establishment of the initial heartbeat and pacemaker and further how morphogenesis and function collaboratively drive heart maturation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"94 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}