Pub Date : 2025-04-02DOI: 10.1016/j.tibs.2025.03.008
Songtao Ye, Choon Leng So, Danfeng Cai
Cellular protein compartmentalization is essential for function, yet the mechanisms directing proteins to their correct destinations remain unclear. Recently, Kilgore, Chinn, Mikhael, and Mitnikov et al. 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.
{"title":"Cracking the protein compartmentalization code with ProtGPS.","authors":"Songtao Ye, Choon Leng So, Danfeng Cai","doi":"10.1016/j.tibs.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.03.008","url":null,"abstract":"<p><p>Cellular protein compartmentalization is essential for function, yet the mechanisms directing proteins to their correct destinations remain unclear. Recently, Kilgore, Chinn, Mikhael, and Mitnikov et al. 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.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-04-02","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}
Pub Date : 2025-04-01DOI: 10.1016/j.tibs.2025.01.006
Rebecca K. Spangler , Keya Jonnalagadda , Jordan D. Ward , Carrie L. Partch
Biological timing mechanisms are intrinsic to all organisms, orchestrating the temporal coordination of biological events through complex genetic networks. Circadian rhythms and developmental timers utilize distinct timekeeping mechanisms. This review summarizes the molecular basis for circadian rhythms in mammals and Drosophila, and recent work leveraging these clocks to understand temporal regulation in Caenorhabditis elegans development. We describe the evolutionary connections between distinct timing mechanisms and discuss recent insights into the rewiring of core clock components in development. By integrating findings from circadian and developmental studies with biochemical and structural analyses of conserved components, we aim to illuminate the molecular basis of nematode timing mechanisms and highlight broader insights into biological timing across species.
{"title":"A wrinkle in timers: evolutionary rewiring of conserved biological timekeepers","authors":"Rebecca K. Spangler , Keya Jonnalagadda , Jordan D. Ward , Carrie L. Partch","doi":"10.1016/j.tibs.2025.01.006","DOIUrl":"10.1016/j.tibs.2025.01.006","url":null,"abstract":"<div><div>Biological timing mechanisms are intrinsic to all organisms, orchestrating the temporal coordination of biological events through complex genetic networks. Circadian rhythms and developmental timers utilize distinct timekeeping mechanisms. This review summarizes the molecular basis for circadian rhythms in mammals and <em>Drosophila</em>, and recent work leveraging these clocks to understand temporal regulation in <em>Caenorhabditis elegans</em> development. We describe the evolutionary connections between distinct timing mechanisms and discuss recent insights into the rewiring of core clock components in development. By integrating findings from circadian and developmental studies with biochemical and structural analyses of conserved components, we aim to illuminate the molecular basis of nematode timing mechanisms and highlight broader insights into biological timing across species.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 344-355"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.tibs.2025.01.010
Jakob K. Reinhardt , David Craft , Jing-Ke Weng
Elucidating plant biosynthetic pathways is key to advancing a sustainable bioeconomy by enabling access to complex natural products through synthetic biology. Despite progress from genomic, transcriptomic, and metabolomic approaches, much multiomics data remain underutilized. This review highlights state-of-the-art multiomics strategies for discovering plant biosynthetic pathways, addressing challenges in data acquisition and interpretation with emerging computational tools. We propose an integrated workflow combining molecular networking, reaction pair analysis, and gene expression patterns to enhance data utilization. Additionally, artificial intelligence (AI)-driven approaches promise to revolutionize pathway discovery by streamlining data analysis and validation. Integrating multiomics data, chemical insights, and advanced algorithms can accelerate understanding of plant metabolism and bioengineering valuable natural products efficiently.
{"title":"Toward an integrated omics approach for plant biosynthetic pathway discovery in the age of AI","authors":"Jakob K. Reinhardt , David Craft , Jing-Ke Weng","doi":"10.1016/j.tibs.2025.01.010","DOIUrl":"10.1016/j.tibs.2025.01.010","url":null,"abstract":"<div><div>Elucidating plant biosynthetic pathways is key to advancing a sustainable bioeconomy by enabling access to complex natural products through synthetic biology. Despite progress from genomic, transcriptomic, and metabolomic approaches, much multiomics data remain underutilized. This review highlights state-of-the-art multiomics strategies for discovering plant biosynthetic pathways, addressing challenges in data acquisition and interpretation with emerging computational tools. We propose an integrated workflow combining molecular networking, reaction pair analysis, and gene expression patterns to enhance data utilization. Additionally, artificial intelligence (AI)-driven approaches promise to revolutionize pathway discovery by streamlining data analysis and validation. Integrating multiomics data, chemical insights, and advanced algorithms can accelerate understanding of plant metabolism and bioengineering valuable natural products efficiently.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 311-321"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The majority of eukaryotic proteins undergo N-terminal (Nt) modifications facilitated by various enzymes. These enzymes, which target the initial amino acid of a polypeptide in a sequence-dependent manner, encompass peptidases, transferases, cysteine oxygenases, and ligases. Nt modifications – such as acetylation, fatty acylations, methylation, arginylation, and oxidation – enhance proteome complexity and regulate protein targeting, stability, and complex formation. Modifications at protein N termini are thereby core components of a large number of biological processes, including cell signaling and motility, autophagy regulation, and plant and animal oxygen sensing. Dysregulation of Nt-modifying enzymes is implicated in several human diseases. In this feature review we provide an overview of the various protein Nt modifications occurring either co- or post-translationally, the enzymes involved, and the biological impact.
{"title":"Protein N-terminal modifications: molecular machineries and biological implications","authors":"Hanne Øye , Malin Lundekvam , Alessia Caiella , Monica Hellesvik , Thomas Arnesen","doi":"10.1016/j.tibs.2024.12.012","DOIUrl":"10.1016/j.tibs.2024.12.012","url":null,"abstract":"<div><div>The majority of eukaryotic proteins undergo N-terminal (Nt) modifications facilitated by various enzymes. These enzymes, which target the initial amino acid of a polypeptide in a sequence-dependent manner, encompass peptidases, transferases, cysteine oxygenases, and ligases. Nt modifications – such as acetylation, fatty acylations, methylation, arginylation, and oxidation – enhance proteome complexity and regulate protein targeting, stability, and complex formation. Modifications at protein N termini are thereby core components of a large number of biological processes, including cell signaling and motility, autophagy regulation, and plant and animal oxygen sensing. Dysregulation of Nt-modifying enzymes is implicated in several human diseases. In this feature review we provide an overview of the various protein Nt modifications occurring either co- or post-translationally, the enzymes involved, and the biological impact.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 290-310"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Post-translational modifications of nucleocytoplasmic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) and O-linked fucose (O-fucose) are emerging as key signaling mechanisms in plants. O-fucosylation and O-GlcNAcylation are catalyzed by SPINDLY (SPY) and SECRET AGENT (SEC), respectively, which are redundantly essential for viability and growth yet function antagonistically or independently in specific developmental contexts. Proteomic studies have identified hundreds of O-GlcNAcylated and O-fucosylated nucleocytoplasmic proteins, revealing their regulatory roles and intersections with phosphorylation pathways that mediate nutrient and hormone signaling. Functional studies on O-glycosylated proteins demonstrate diverse impacts on protein activity and biological processes. Together, O-fucosylation, O-GlcNAcylation, and phosphorylation form a regulatory network that controls plant growth, development, and acclimation. This review highlights recent progress and outlines future directions in studying O-fucosylation and O-GlcNAcylation in plants.
{"title":"A tale of two sugars: O-GlcNAc and O-fucose orchestrate growth, development, and acclimation in plants","authors":"Yalikunjiang Aizezi , Yizhong Yuan , Shou-Ling Xu , Zhi-Yong Wang","doi":"10.1016/j.tibs.2025.01.003","DOIUrl":"10.1016/j.tibs.2025.01.003","url":null,"abstract":"<div><div>Post-translational modifications of nucleocytoplasmic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) and O-linked fucose (O-fucose) are emerging as key signaling mechanisms in plants. O-fucosylation and O-GlcNAcylation are catalyzed by SPINDLY (SPY) and SECRET AGENT (SEC), respectively, which are redundantly essential for viability and growth yet function antagonistically or independently in specific developmental contexts. Proteomic studies have identified hundreds of O-GlcNAcylated and O-fucosylated nucleocytoplasmic proteins, revealing their regulatory roles and intersections with phosphorylation pathways that mediate nutrient and hormone signaling. Functional studies on O-glycosylated proteins demonstrate diverse impacts on protein activity and biological processes. Together, O-fucosylation, O-GlcNAcylation, and phosphorylation form a regulatory network that controls plant growth, development, and acclimation. This review highlights recent progress and outlines future directions in studying O-fucosylation and O-GlcNAcylation in plants.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 332-343"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397654","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}
Pub Date : 2025-04-01DOI: 10.1016/S0968-0004(25)00066-0
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/S0968-0004(25)00066-0","DOIUrl":"10.1016/S0968-0004(25)00066-0","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages i-ii"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/j.tibs.2025.01.002
Rajeev Kumar
Homologous recombination (HR) is critical for maintaining genome stability, relying on RAD51 recombinase to catalyze homology-dependent accurate DNA repair. While various cellular modulators control HR, Carver, Yu, et al. reveal a unique molecular mechanism used by FIDGETIN-LIKE-1 (FIGNL1) that dissociates RAD51 from DNA through RAD51 N terminus and FIGNL1 hexamer assembly.
{"title":"FIGNL1 hexamer dissociates RAD51-filament: a new mechanism","authors":"Rajeev Kumar","doi":"10.1016/j.tibs.2025.01.002","DOIUrl":"10.1016/j.tibs.2025.01.002","url":null,"abstract":"<div><div>Homologous recombination (HR) is critical for maintaining genome stability, relying on RAD51 recombinase to catalyze homology-dependent accurate DNA repair. While various cellular modulators control HR, <span><span>Carver, Yu, <em>et al.</em></span><svg><path></path></svg></span> reveal a unique molecular mechanism used by FIDGETIN-LIKE-1 (FIGNL1) that dissociates RAD51 from DNA through RAD51 N terminus and FIGNL1 hexamer assembly.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 287-289"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073265","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}
Pub Date : 2025-04-01DOI: 10.1016/j.tibs.2025.01.008
Marissa Coppola , Tessa O. House , Jessica W. Tsai
For new laboratories, maintaining pricing within a budget while obtaining the necessary supplies and reagents for experiments can feel daunting. In this article, we highlight a practical guide to negotiating the best pricing for your laboratory. Using these approaches enables scientists to be fiscally responsible stewards of grant funding.
{"title":"Maximizing grant funding: strategies for negotiating laboratory pricing","authors":"Marissa Coppola , Tessa O. House , Jessica W. Tsai","doi":"10.1016/j.tibs.2025.01.008","DOIUrl":"10.1016/j.tibs.2025.01.008","url":null,"abstract":"<div><div>For new laboratories, maintaining pricing within a budget while obtaining the necessary supplies and reagents for experiments can feel daunting. In this article, we highlight a practical guide to negotiating the best pricing for your laboratory. Using these approaches enables scientists to be fiscally responsible stewards of grant funding.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 281-284"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432154","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}
Pub Date : 2025-04-01DOI: 10.1016/S0968-0004(25)00069-6
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/S0968-0004(25)00069-6","DOIUrl":"10.1016/S0968-0004(25)00069-6","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Page e1"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760350","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}
Pub Date : 2025-04-01DOI: 10.1016/j.tibs.2025.01.007
Shweta Chitkara , G. Ekin Atilla-Gokcumen
Recent studies emphasize that lipid synthesis, metabolism, and transport are crucial in modulating lipid function, underscoring the significance of lipid localization within the cell, in addition to their chemical structure. Ceramides stand out in this context because of their multifaceted roles in cellular processes. Here, we focus on the role of ceramides in apoptosis, senescence, and autophagy as these processes offer unique and contrasting perspectives on how ceramides function and can be intricately linked to their subcellular localization, providing critical insights into their complex biological interactions. Additionally, we highlight recent advancements in tools and techniques that have boosted our understanding of ceramide dynamics and different mechanisms of lipid functioning.
{"title":"Decoding ceramide function: how localization shapes cellular fate and how to study it","authors":"Shweta Chitkara , G. Ekin Atilla-Gokcumen","doi":"10.1016/j.tibs.2025.01.007","DOIUrl":"10.1016/j.tibs.2025.01.007","url":null,"abstract":"<div><div>Recent studies emphasize that lipid synthesis, metabolism, and transport are crucial in modulating lipid function, underscoring the significance of lipid localization within the cell, in addition to their chemical structure. Ceramides stand out in this context because of their multifaceted roles in cellular processes. Here, we focus on the role of ceramides in apoptosis, senescence, and autophagy as these processes offer unique and contrasting perspectives on how ceramides function and can be intricately linked to their subcellular localization, providing critical insights into their complex biological interactions. Additionally, we highlight recent advancements in tools and techniques that have boosted our understanding of ceramide dynamics and different mechanisms of lipid functioning.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 4","pages":"Pages 356-367"},"PeriodicalIF":11.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497868","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}
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