Pub Date : 2026-02-05DOI: 10.1016/j.molcel.2026.01.014
Coordination and collaboration between biological systems is shaped over time by environmental pressures. Collaborations between scientists also evolve and grow in directions that would have been hard to predict from their outset. Sara Miller spoke with Felicia Basilicata and Claudia Keller Valsecchi about their long-term collaboration. The two started working together as postdocs and started their independent groups in Mainz, Germany and are now navigating continued collaboration after relocating to institutions in different cities. How do you start a collaboration and maintain it, even when you don't always agree? An edited version of this conversation is presented below.
{"title":"Fun fuels collaboration.","authors":"","doi":"10.1016/j.molcel.2026.01.014","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.014","url":null,"abstract":"<p><p>Coordination and collaboration between biological systems is shaped over time by environmental pressures. Collaborations between scientists also evolve and grow in directions that would have been hard to predict from their outset. Sara Miller spoke with Felicia Basilicata and Claudia Keller Valsecchi about their long-term collaboration. The two started working together as postdocs and started their independent groups in Mainz, Germany and are now navigating continued collaboration after relocating to institutions in different cities. How do you start a collaboration and maintain it, even when you don't always agree? An edited version of this conversation is presented below.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"86 3","pages":"425-428"},"PeriodicalIF":16.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132367","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 : 2026-02-04DOI: 10.1016/j.molcel.2026.01.005
Carlos Origel Marmolejo, Celina Sanchez, Erin Helms, Melissa J. McEvoy, Juyoung Lee, Marcel Werner, Paige Roberts, Stephan Hamperl, Joshua C. Saldivar
Transcription condensates are liquid-like compartments where transcription factors, co-activators, and RNA polymerases are selectively enriched and regulate transcription initiation of associated genes. While the principles governing the enrichment of proteins within transcription condensates are being elucidated, mechanisms that coordinate condensate dynamics with other nuclear processes, such as DNA replication, have not been identified. We show in human cells that at the G1/S cell-cycle transition, large transcription condensates form at histone locus bodies (HLBs) in a cyclin-dependent kinase 1 and 2 (CDK1/2)-dependent manner. By mid-S phase, ataxia-telangiectasia and Rad3-related kinase (ATR) accumulates within HLBs and dissolves the associated condensates via its downstream effector, CHK1. Failure to dissolve condensates results in overexpression of linker H1 histones and nucleus-wide DNA damage. Moreover, an imbalance in the different linker histones accentuates DNA damage in ATR-CHK1-deficient cells. Our work reveals how transcription condensates are precisely controlled in the S phase to fine-tune gene activation and safeguard genome stability.
{"title":"Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability","authors":"Carlos Origel Marmolejo, Celina Sanchez, Erin Helms, Melissa J. McEvoy, Juyoung Lee, Marcel Werner, Paige Roberts, Stephan Hamperl, Joshua C. Saldivar","doi":"10.1016/j.molcel.2026.01.005","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.005","url":null,"abstract":"Transcription condensates are liquid-like compartments where transcription factors, co-activators, and RNA polymerases are selectively enriched and regulate transcription initiation of associated genes. While the principles governing the enrichment of proteins within transcription condensates are being elucidated, mechanisms that coordinate condensate dynamics with other nuclear processes, such as DNA replication, have not been identified. We show in human cells that at the G1/S cell-cycle transition, large transcription condensates form at histone locus bodies (HLBs) in a cyclin-dependent kinase 1 and 2 (CDK1/2)-dependent manner. By mid-S phase, ataxia-telangiectasia and Rad3-related kinase (ATR) accumulates within HLBs and dissolves the associated condensates via its downstream effector, CHK1. Failure to dissolve condensates results in overexpression of linker H1 histones and nucleus-wide DNA damage. Moreover, an imbalance in the different linker histones accentuates DNA damage in ATR-CHK1-deficient cells. Our work reveals how transcription condensates are precisely controlled in the S phase to fine-tune gene activation and safeguard genome stability.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"288 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122465","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 : 2026-02-03DOI: 10.1016/j.molcel.2026.01.027
Hao Feng, Kai Shao, Zhifeng Zeng, Eddie Yong Jun Tan, Zeyu Hu, Ruiliang Zhao, Jikai Rao, Jian Shi, Zhuojian Chen, Rafael Pinilla Redondo, Bin Wu, Wenyuan Han, Min Luo
{"title":"Filament-mediated repurposing of toxic dITP for immunity in the Kongming system","authors":"Hao Feng, Kai Shao, Zhifeng Zeng, Eddie Yong Jun Tan, Zeyu Hu, Ruiliang Zhao, Jikai Rao, Jian Shi, Zhuojian Chen, Rafael Pinilla Redondo, Bin Wu, Wenyuan Han, Min Luo","doi":"10.1016/j.molcel.2026.01.027","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.027","url":null,"abstract":"","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"21 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110774","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 : 2026-01-28DOI: 10.1016/j.molcel.2026.01.008
Anna Meichsner, Verian Bader, Konstanze F. Winklhofer
{"title":"Mitochondria as sources and targets of cellular signaling","authors":"Anna Meichsner, Verian Bader, Konstanze F. Winklhofer","doi":"10.1016/j.molcel.2026.01.008","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.008","url":null,"abstract":"","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"280 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072071","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 : 2026-01-28DOI: 10.1016/j.molcel.2026.01.007
Isabella R. Lawrence, Emily C. Sutton, Shivang Bhaskar, Susan J. Baserga
{"title":"Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus","authors":"Isabella R. Lawrence, Emily C. Sutton, Shivang Bhaskar, Susan J. Baserga","doi":"10.1016/j.molcel.2026.01.007","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.007","url":null,"abstract":"","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"44 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072072","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 : 2026-01-28DOI: 10.1016/j.molcel.2026.01.011
Aakriti Jain, Roberto Zoncu
{"title":"Lysosomes as hubs of metabolic sensing and cellular homeostasis","authors":"Aakriti Jain, Roberto Zoncu","doi":"10.1016/j.molcel.2026.01.011","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.011","url":null,"abstract":"","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"217 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072070","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 : 2026-01-28DOI: 10.1016/j.molcel.2026.01.006
Yoseop Yoon, Cailyx Quan, Lindsey V. Soles, Yongsheng Shi
mRNA maturation requires precise coordination among transcription, 5′ capping, splicing, and 3′ end formation. Recent biochemical, structural, and genomic studies demonstrate that these processes are tightly coupled through dynamic interactions among RNA polymerase II, the spliceosome, and cleavage–polyadenylation complexes. Here, we synthesize current mechanistic insights into how transcription elongation factors and RNA processing machineries communicate to ensure efficient and accurate transcript maturation. We propose a “U1 relay” model as a unified framework for understanding co-transcriptional splicing and 3′ end formation. We further discuss how RNAs are sorted into nuclear retention/degradation or export pathways based on the RNA processing status. Importantly, RNA processing factors not only act downstream of transcription but also feed back to modulate transcriptional elongation, pausing, and termination, thereby reinforcing bidirectional coupling between RNA synthesis and processing.
{"title":"Coordinating mRNA maturation: The U1 relay model","authors":"Yoseop Yoon, Cailyx Quan, Lindsey V. Soles, Yongsheng Shi","doi":"10.1016/j.molcel.2026.01.006","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.006","url":null,"abstract":"mRNA maturation requires precise coordination among transcription, 5′ capping, splicing, and 3′ end formation. Recent biochemical, structural, and genomic studies demonstrate that these processes are tightly coupled through dynamic interactions among RNA polymerase II, the spliceosome, and cleavage–polyadenylation complexes. Here, we synthesize current mechanistic insights into how transcription elongation factors and RNA processing machineries communicate to ensure efficient and accurate transcript maturation. We propose a “U1 relay” model as a unified framework for understanding co-transcriptional splicing and 3′ end formation. We further discuss how RNAs are sorted into nuclear retention/degradation or export pathways based on the RNA processing status. Importantly, RNA processing factors not only act downstream of transcription but also feed back to modulate transcriptional elongation, pausing, and termination, thereby reinforcing bidirectional coupling between RNA synthesis and processing.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"43 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070577","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 : 2026-01-28DOI: 10.1016/j.molcel.2026.01.001
Guanyu Chen, Hangyu Dong, Ye Tian
The co-evolution of mitochondria and the nucleus established constant mito-nuclear communication that is essential for both cellular and organismal homeostasis. At the cell-autonomous level, mitochondrial perturbations activate retrograde pathways such as the mitochondrial unfolded protein response (UPRmt) and the mitochondrial integrated stress response (ISRmt), which couple organelle dysfunction to nuclear transcriptional programs, thereby promoting mitochondrial function and preserving cellular integrity. Importantly, this communication is not confined to individual cells but extends across tissues to coordinate systemic adaptations. Stress signals can be sensed, broadcasted through secreted mitokines and neural circuits, and then interpreted by distal organs to coordinate systemic adaptations. These systemic responses integrate metabolism, immunity, and behavior, conferring resilience to stress and shaping the trajectory of aging. Understanding this multi-layered communication, from the organelle to the organism and its microbial ecosystem, promises new therapeutic strategies to enhance mitochondrial function, promote resilience, and extend healthspan.
{"title":"Mito-nuclear communication: From cellular responses to organismal health","authors":"Guanyu Chen, Hangyu Dong, Ye Tian","doi":"10.1016/j.molcel.2026.01.001","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.001","url":null,"abstract":"The co-evolution of mitochondria and the nucleus established constant mito-nuclear communication that is essential for both cellular and organismal homeostasis. At the cell-autonomous level, mitochondrial perturbations activate retrograde pathways such as the mitochondrial unfolded protein response (UPR<sup>mt</sup>) and the mitochondrial integrated stress response (ISR<sup>mt</sup>), which couple organelle dysfunction to nuclear transcriptional programs, thereby promoting mitochondrial function and preserving cellular integrity. Importantly, this communication is not confined to individual cells but extends across tissues to coordinate systemic adaptations. Stress signals can be sensed, broadcasted through secreted mitokines and neural circuits, and then interpreted by distal organs to coordinate systemic adaptations. These systemic responses integrate metabolism, immunity, and behavior, conferring resilience to stress and shaping the trajectory of aging. Understanding this multi-layered communication, from the organelle to the organism and its microbial ecosystem, promises new therapeutic strategies to enhance mitochondrial function, promote resilience, and extend healthspan.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"72 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146057098","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 : 2026-01-27DOI: 10.1016/j.molcel.2026.01.002
D. Dierks, S. Schwartz
N6-methyladenosine (m⁶A) is the most abundant internal modification of mRNA and is most strongly linked to promoting mRNA decay. Why transcripts are born with a death-promoting mark has remained unclear. A previously proposed "fast-track" model posited regulated, gene-specific modulation of m⁶A to coordinate translation and turnover. However, emerging evidence reveals that m⁶A is broadly and mostly constitutively installed at all DRACH motifs except in the vicinity of splice sites, all of which challenge a fast-track model. We propose an "m⁶A surveillance model": properly spliced transcripts mostly evade methylation, while unspliced, transposon-derived, viral, or aberrant RNAs are hypermethylated and selectively degraded. This model reframes m⁶A as a default quality-control mark that flags undesirable unspliced RNAs for removal. We discuss literature supporting and challenging this model as well as experimental priorities that could allow for a more thorough investigation of this model.
{"title":"Why m⁶A? An RNA surveillance model","authors":"D. Dierks, S. Schwartz","doi":"10.1016/j.molcel.2026.01.002","DOIUrl":"https://doi.org/10.1016/j.molcel.2026.01.002","url":null,"abstract":"N6-methyladenosine (m⁶A) is the most abundant internal modification of mRNA and is most strongly linked to promoting mRNA decay. Why transcripts are born with a death-promoting mark has remained unclear. A previously proposed \"fast-track\" model posited regulated, gene-specific modulation of m⁶A to coordinate translation and turnover. However, emerging evidence reveals that m⁶A is broadly and mostly constitutively installed at all DRACH motifs except in the vicinity of splice sites, all of which challenge a fast-track model. We propose an \"m⁶A surveillance model\": properly spliced transcripts mostly evade methylation, while unspliced, transposon-derived, viral, or aberrant RNAs are hypermethylated and selectively degraded. This model reframes m⁶A as a default quality-control mark that flags undesirable unspliced RNAs for removal. We discuss literature supporting and challenging this model as well as experimental priorities that could allow for a more thorough investigation of this model.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"71 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072075","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号