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Molecular mechanisms and biotechnology applications of CRISPR-Cas12a. CRISPR-Cas12a的分子机制及生物技术应用
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-27 DOI: 10.1038/s41580-026-00969-x
Aakash Saha,Rodrigo Fregoso Ocampo,Jacquelyn T Wright,David W Taylor,Giulia Palermo
{"title":"Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.","authors":"Aakash Saha,Rodrigo Fregoso Ocampo,Jacquelyn T Wright,David W Taylor,Giulia Palermo","doi":"10.1038/s41580-026-00969-x","DOIUrl":"https://doi.org/10.1038/s41580-026-00969-x","url":null,"abstract":"CRISPR-Cas12a is a versatile RNA-guided nuclease that has rapidly gained prominence for its dual functionality in genome editing and nucleic acid detection. In this Review, we discuss the structural, biochemical and mechanistic features of Cas12a that underpin its autonomous processing of the guide RNA and indiscriminate cleavage of single-stranded DNA, which enable Cas12a applications ranging from gene therapy to rapid diagnostics. We discuss key allosteric regulators and functional modules that orchestrate Cas12a activity, focusing on the core regulatory structural elements that control maturation of the guide RNA, target specificity, and both cis-cleavage and trans-cleavage activities, including the determinants of off-target cleavage. We provide a comparative analysis of Cas12a and the widely used Cas9, which further illuminates the distinctive attributes of Cas12a, and discuss recent advances in the characterization of its orthologues and in the development of engineered variants that expand its capabilities. Collectively, we present a comprehensive understanding of Cas12a and its increasing impact on biotechnology, therapeutics and molecular diagnostics.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753065","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}
引用次数: 0
The PANoptosis hypothesis examined. 检查PANoptosis假说。
IF 90.2 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-21 DOI: 10.1038/s41580-026-00970-4
James E Vince, John Silke
{"title":"The PANoptosis hypothesis examined.","authors":"James E Vince, John Silke","doi":"10.1038/s41580-026-00970-4","DOIUrl":"https://doi.org/10.1038/s41580-026-00970-4","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":90.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777008","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}
引用次数: 0
The regulation, function and disease relevance of cytoplasmic tRNAs. 胞质trna的调控、功能和疾病相关性。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-21 DOI: 10.1038/s41580-026-00963-3
Robin E Stanley,Todd M Lowe,Zoya Ignatova
{"title":"The regulation, function and disease relevance of cytoplasmic tRNAs.","authors":"Robin E Stanley,Todd M Lowe,Zoya Ignatova","doi":"10.1038/s41580-026-00963-3","DOIUrl":"https://doi.org/10.1038/s41580-026-00963-3","url":null,"abstract":"Transfer RNAs (tRNAs) are core components of protein synthesis. Recent studies and technological advances have expanded our understanding of the complexities of tRNA biology. In this Review, we discuss the genomic organization and spatiotemporal expression of human cytoplasmic tRNAs, the quality control pathways that govern their maturation and functionality, and how dysregulation of tRNA biogenesis and function contributes to human pathologies. We also present emerging concepts regarding how tissue-specific tRNA abundance regulates translation velocity and how tRNAs are centrally involved in surveillance and stress signalling pathways, including ribosome-associated quality control and the integrated stress response. We further discuss the potential of tRNA-based therapeutics, highlighting new strategies to address tRNA-associated translation defects. By bridging between molecular tRNA biology and its clinical implications, we emphasize the crucial need to understand the intricacies of tRNA regulation in order to therapeutically target them in a variety of diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"29 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731378","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}
引用次数: 0
Prevailing views of cell senescence overlook its biological complexity. 细胞衰老的主流观点忽视了它的生物学复杂性。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-20 DOI: 10.1038/s41580-026-00973-1
Nadine Martin,Han Li,William M Keyes,David Bernard
{"title":"Prevailing views of cell senescence overlook its biological complexity.","authors":"Nadine Martin,Han Li,William M Keyes,David Bernard","doi":"10.1038/s41580-026-00973-1","DOIUrl":"https://doi.org/10.1038/s41580-026-00973-1","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"16 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726247","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}
引用次数: 0
In-cell chemistry enables discovery of cyclic peptide transcription factor inhibitors. 细胞内化学可以发现环肽转录因子抑制剂。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-14 DOI: 10.1038/s41580-026-00971-3
Andrew Brennan
{"title":"In-cell chemistry enables discovery of cyclic peptide transcription factor inhibitors.","authors":"Andrew Brennan","doi":"10.1038/s41580-026-00971-3","DOIUrl":"https://doi.org/10.1038/s41580-026-00971-3","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"309 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680720","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}
引用次数: 0
Harnessing ER-associated degradation to target transmembrane proteins. 利用内质网相关降解靶向跨膜蛋白。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-10 DOI: 10.1038/s41580-026-00966-0
Wei Wang,Haikun Song
{"title":"Harnessing ER-associated degradation to target transmembrane proteins.","authors":"Wei Wang,Haikun Song","doi":"10.1038/s41580-026-00966-0","DOIUrl":"https://doi.org/10.1038/s41580-026-00966-0","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"28 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648872","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}
引用次数: 0
Turing equations capture living skin patterns. 图灵方程式捕捉活体皮肤模式。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-10 DOI: 10.1038/s41580-026-00972-2
Maksim V Plikus
{"title":"Turing equations capture living skin patterns.","authors":"Maksim V Plikus","doi":"10.1038/s41580-026-00972-2","DOIUrl":"https://doi.org/10.1038/s41580-026-00972-2","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"333 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648873","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}
引用次数: 0
Phase separation across membranes and condensates in cell organization and function. 跨膜的相分离和细胞组织和功能的凝聚。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-09 DOI: 10.1038/s41580-026-00961-5
Agustín Mangiarotti,Rumiana Dimova
{"title":"Phase separation across membranes and condensates in cell organization and function.","authors":"Agustín Mangiarotti,Rumiana Dimova","doi":"10.1038/s41580-026-00961-5","DOIUrl":"https://doi.org/10.1038/s41580-026-00961-5","url":null,"abstract":"Phase separation is a fundamental principle of cellular organization that typically leads to two coexisting phases: a dense one, where intermolecular interactions are stronger and molecules are more tightly packed, and a dilute, less packed phase, with weaker interactions and lower molecular concentration. This process drives the formation of both lateral membrane domains (rafts) and liquid-like protein and nucleic acid condensates. This Review explores the dynamic interplay between biomolecular condensates and membrane lipid domains and how phase separation occurs in the three-dimensional (bulk) cellular interior and at two-dimensional membrane interfaces. We examine how membranes act as platforms influencing condensate formation and function and, conversely, how condensates modulate membrane properties and organization. By highlighting diverse examples from cell signalling, tight-junction assembly and stress responses, we emphasize how these coupled interactions are crucial for cellular organization, function and fitness.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"32 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641384","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}
引用次数: 0
Nuclear speckles of GC richness GC丰度的核斑
IF 90.2 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-03 DOI: 10.1038/s41580-026-00965-1
Eytan Zlotorynski
{"title":"Nuclear speckles of GC richness","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-026-00965-1","DOIUrl":"10.1038/s41580-026-00965-1","url":null,"abstract":"Nuclear speckles support the splicing of levelled exon–intron architecture transcripts, and their evolution shaped genome organization in amniotes.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 5","pages":"342-342"},"PeriodicalIF":90.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611918","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}
引用次数: 0
Programming novel intrinsically disordered proteins by directed evolution. 通过定向进化编程新的内在无序蛋白质。
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2026-04-02 DOI: 10.1038/s41580-026-00968-y
Yuefeng Ma
{"title":"Programming novel intrinsically disordered proteins by directed evolution.","authors":"Yuefeng Ma","doi":"10.1038/s41580-026-00968-y","DOIUrl":"https://doi.org/10.1038/s41580-026-00968-y","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"120 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599469","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}
引用次数: 0
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