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RNA processing in innate immunity: regulation by RNA-binding proteins. 先天免疫中的RNA加工：RNA结合蛋白的调控。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-15 DOI: 10.1016/j.tibs.2025.04.004
Asmita Panthi, Kristen W Lynch
{"title":"RNA processing in innate immunity: regulation by RNA-binding proteins.","authors":"Asmita Panthi, Kristen W Lynch","doi":"10.1016/j.tibs.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.04.004","url":null,"abstract":"<p><p>RNA processing is an important but often overlooked process in determining protein expression. Alternative polyadenylation and regulated mRNA stability control the amount and duration of protein expression, while alternative splicing also controls protein identity and function. Much work in innate immunity has focused on the activation of transcription factors and the downstream consequences in gene expression. However, there is increasing evidence indicating that regulation of RNA processing by RNA-binding proteins (RBPs) contributes significantly to tuning the innate immune response. Herein we review work highlighting the impact of RNA processing in innate immunity and describe the RBPs and mechanisms driving this regulation. We conclude with a discussion of unanswered questions to motivate continued research in this important and understudied field.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085599","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
Accelerating the stride toward functional glycoproteomics. 加速向功能性糖蛋白组学迈进。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-09 DOI: 10.1016/j.tibs.2025.04.002
Tim S Veth, Nicholas M Riley
{"title":"Accelerating the stride toward functional glycoproteomics.","authors":"Tim S Veth, Nicholas M Riley","doi":"10.1016/j.tibs.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.04.002","url":null,"abstract":"<p><p>The heterogeneity of the glycoproteome and the challenges associated with quantifying its regulation in complex biological systems have hindered functional glycoproteomics. The deep quantitative glycoprofiling (DQGlyco) method recently developed by Potel, Burtscher, and Garrido-Rodriguez et al. significantly improves the glycoproteomic depth compared with existing methods, aiding our ability to interrogate the functional implications of glycoproteins.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955285","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
Engineering RiPP pathways: strategies for generating complex bioactive peptides. 工程RiPP途径：生成复杂生物活性肽的策略。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-06 DOI: 10.1016/j.tibs.2025.04.001
Ayoola B Smith, Renee C Ejindu, Jonathan R Chekan
{"title":"Engineering RiPP pathways: strategies for generating complex bioactive peptides.","authors":"Ayoola B Smith, Renee C Ejindu, Jonathan R Chekan","doi":"10.1016/j.tibs.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.04.001","url":null,"abstract":"<p><p>Historically, natural products have been essential sources of therapeutic agents, many of which are currently used to manage various diseases. In recent years, ribosomally synthesized and post-translationally modified peptides (RiPPs) have garnered considerable interest in drug discovery and development due to their biosynthetic plasticity and their ability to generate diverse bioactive structural scaffolds. Unfortunately, many RiPPs have suboptimal bioavailability and proteolytic stability, significantly limiting their clinical potential. Moreover, the complexity of RiPP structures makes total synthesis extremely difficult. These drawbacks necessitate pathway engineering to create derivatives with potentially optimized physicochemical properties. Herein, we review recent efforts to surmount pathway engineering challenges and to rationally modify components of RiPP pathways for new functions to derive new bioactive analogs.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960087","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
Sensitivity to chirality correlates in a continuum with protein disorder. 对手性的敏感性与蛋白质紊乱连续相关。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-02 DOI: 10.1016/j.tibs.2025.04.003
Lucía Álvarez, Lucía Beatriz Chemes
{"title":"Sensitivity to chirality correlates in a continuum with protein disorder.","authors":"Lucía Álvarez, Lucía Beatriz Chemes","doi":"10.1016/j.tibs.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.04.003","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) exist as dynamic conformational ensembles the behavior of which challenges the tenets of the protein structure-function paradigm. In a new study, Newcombe, Due et al. reveal a striking continuum in sensitivity to chirality: while folded complexes are under strong chiral constraints, progressively disordered complexes show decreased sensitivity to chirality.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959696","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
Small RNA and Toll-like receptor interactions: origins and disease mechanisms 小RNA和toll样受体相互作用：起源和疾病机制。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/j.tibs.2025.01.004
Jiancheng Yu , Xudong Zhang , Chen Cai , Tong Zhou , Qi Chen
{"title":"Small RNA and Toll-like receptor interactions: origins and disease mechanisms","authors":"Jiancheng Yu ,&nbsp;Xudong Zhang ,&nbsp;Chen Cai ,&nbsp;Tong Zhou ,&nbsp;Qi Chen","doi":"10.1016/j.tibs.2025.01.004","DOIUrl":"10.1016/j.tibs.2025.01.004","url":null,"abstract":"<div><div>Advances in small RNA sequencing have revealed diverse small noncoding RNAs (sncRNAs) beyond microRNAs (miRNAs), derived from transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and Y RNAs, carrying distinct RNA modifications. These emerging sncRNAs can function beyond RNA interference (RNAi), adopting aptamer-like roles by interacting with Toll-like receptors 7 and 8 (TLR7 and TLR8) via specific sequences, modifications, and structures. We propose a Sequential Activation Hypothesis where initial abnormal sncRNAs – triggered by infections or stresses – activate TLR7/8, leading to autoantibody production against autoantigens like RNA-binding proteins La and Ro. These autoantibody–antigen complexes further promote secondary immunogenic sncRNA production and repetitive TLR7/8 activation, perpetuating a vicious cycle sustaining autoimmunity. TLR7/8's X chromosome location and sex-biased expression contribute to female-dominant autoimmune diseases. Understanding sncRNA–TLR interactions is essential for designing novel therapeutic strategies.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Pages 385-401"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432156","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
Rethinking transcription factor dynamics and transcription regulation in eukaryotes 真核生物转录因子动力学和转录调控的再思考。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/j.tibs.2025.01.012
Reiner A. Veitia
{"title":"Rethinking transcription factor dynamics and transcription regulation in eukaryotes","authors":"Reiner A. Veitia","doi":"10.1016/j.tibs.2025.01.012","DOIUrl":"10.1016/j.tibs.2025.01.012","url":null,"abstract":"<div><div>Transcription factors (TFs) control gene expression by binding to specific DNA motifs in <em>cis</em>-regulatory elements. Cooperativity has been thought to ensure TF binding specificity. Recent research suggests that, at least in yeast, the role of cooperativity has probably been overemphasized. Consequently, synergy – the collective recruitment of the transcriptional machinery by TFs bound at multiple DNA sites – emerges as a more significant mechanism for achieving the specificity of the transcriptional response. Furthermore, I argue that the concentration of TFs within phase-separated nuclear condensates and their covalent modifications play an underappreciated but crucial role in sharpening transcriptional responses through complementary mechanisms. A model integrating cooperativity, synergy, post-translational modifications, and phase separation provides a comprehensive framework to explain dynamic, context-specific transcriptional responses in eukaryotes.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Pages 376-384"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565561","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
Advisory Board and Contents 咨询委员会及内容
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/S0968-0004(25)00085-4
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/S0968-0004(25)00085-4","DOIUrl":"10.1016/S0968-0004(25)00085-4","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Pages i-ii"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890552","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
Subscription and Copyright Information 订阅及版权资料
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/S0968-0004(25)00088-X
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/S0968-0004(25)00088-X","DOIUrl":"10.1016/S0968-0004(25)00088-X","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Page e1"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891170","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
Cracking the protein compartmentalization code with ProtGPS 用ProtGPS破解蛋白质区隔编码。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/j.tibs.2025.03.008
Songtao Ye , Choon Leng So , Danfeng Cai
{"title":"Cracking the protein compartmentalization code with ProtGPS","authors":"Songtao Ye ,&nbsp;Choon Leng So ,&nbsp;Danfeng Cai","doi":"10.1016/j.tibs.2025.03.008","DOIUrl":"10.1016/j.tibs.2025.03.008","url":null,"abstract":"<div><div>Cellular protein compartmentalization is essential for function, yet the mechanisms directing proteins to their correct destinations remain unclear. Recently, <span><span>Kilgore, Chinn, Mikhael, and Mitnikov <em>et al</em>.</span><svg><path></path></svg></span> introduced ProtGPS, an artificial intelligence (AI) model that recognizes sequence-encoded localization patterns. ProtGPS predicts condensate-targeting sequences, facilitates peptide design, and identifies pathogenic mutations disrupting protein compartmentalization.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Pages 369-371"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778711","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
RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer 迈向代谢反应的RNA催化：核酶催化烷基转移的进展。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-05-01 DOI: 10.1016/j.tibs.2025.01.011
David M.J. Lilley , Lin Huang
{"title":"RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer","authors":"David M.J. Lilley ,&nbsp;Lin Huang","doi":"10.1016/j.tibs.2025.01.011","DOIUrl":"10.1016/j.tibs.2025.01.011","url":null,"abstract":"<div><div>The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by <em>in vitro</em> evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 5","pages":"Pages 417-424"},"PeriodicalIF":11.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584232","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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