Molecular Cell最新文献_第8页

A cut above: Bacterial deubiquitinases with ubiquitin clippase activity 上图：具有泛素剪切酶活性的细菌去泛素酶

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.023

Mark Hochstrasser

引用次数: 0

Unlocking protein networks with Predictomes: The SPOC advantage 用预测因子解锁蛋白质网络：SPOC优势

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.010

Arne Elofsson

引用次数: 0

Autonomous shaping of the piRNA sequence repertoire by competition between adjacent ping-pong amplification sites 邻近乒乓扩增位点之间的竞争自主塑造piRNA序列曲目

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.015

Jie Yu, Fumiko Kawasaki, Natsuko Izumi, Takashi Kiuchi, Susumu Katsuma, Yukihide Tomari, Keisuke Shoji

{"title":"Autonomous shaping of the piRNA sequence repertoire by competition between adjacent ping-pong amplification sites","authors":"Jie Yu, Fumiko Kawasaki, Natsuko Izumi, Takashi Kiuchi, Susumu Katsuma, Yukihide Tomari, Keisuke Shoji","doi":"10.1016/j.molcel.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.015","url":null,"abstract":"PIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements (TEs). In many species, piRNAs are generated via a complex process known as the ping-pong pathway, coupling TE cleavage with piRNA amplification. However, the biological significance of this complexity remains unclear. Here, we systematically compared piRNA profiles in two related silkworm cell lines and found significant changes in their sequence repertoire. Importantly, the changeability of this repertoire negatively correlated with the piRNA biogenesis efficiency, a trend also observed in Drosophila stocks and single silkworm eggs. This can be explained by competition between adjacent ping-pong sites, supported by our mathematical modeling. Moreover, this competition can rationalize how piRNAs autonomously avoid deleterious mismatches to target TEs in silkworms, flies, and mice. These findings unveil the intrinsic plasticity and adaptability of the piRNA system to combat diverse TE sequences and highlight the universal power of competition and self-amplification to drive autonomous optimization.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"61 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660405","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

Isogenic comparison of Airn and Xist reveals core principles of Polycomb recruitment by lncRNAs Airn和Xist的等基因比较揭示了lncrna募集Polycomb的核心原理

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.014

Jackson B. Trotman, Elizabeth W. Abrash, McKenzie M. Murvin, Aki K. Braceros, Shuang Li, Samuel P. Boyson, Ryan T. Salcido, Rachel E. Cherney, Steven R. Bischoff, Kyle Kaufmann, Quinn E. Eberhard, Zhiyue Zhang, Dale O. Cowley, J. Mauro Calabrese

{"title":"Isogenic comparison of Airn and Xist reveals core principles of Polycomb recruitment by lncRNAs","authors":"Jackson B. Trotman, Elizabeth W. Abrash, McKenzie M. Murvin, Aki K. Braceros, Shuang Li, Samuel P. Boyson, Ryan T. Salcido, Rachel E. Cherney, Steven R. Bischoff, Kyle Kaufmann, Quinn E. Eberhard, Zhiyue Zhang, Dale O. Cowley, J. Mauro Calabrese","doi":"10.1016/j.molcel.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.014","url":null,"abstract":"The mechanisms and biological roles of Polycomb repressive complex (PRC) recruitment by long noncoding RNAs (lncRNAs) remain unclear. To gain insight, we expressed two lncRNAs that recruit PRCs to multi-megabase domains, Airn and Xist, from an ectopic locus in mouse stem cells and compared effects. Unexpectedly, ectopic Airn recruited PRC1 and PRC2 to chromatin with a potency resembling Xist yet did not repress genes. Compared with PRC2, PRC1 was more proximal to Airn and Xist, where its enrichment over C-rich elements required the RNA-binding protein HNRNPK. Fusing Airn to Repeat A, the domain required for gene silencing by Xist, enabled gene silencing and altered local patterns but not relative levels of PRC-directed modifications. Our data suggest that, endogenously, Airn recruits PRCs to maintain rather than initiate gene silencing, that PRC recruitment occurs independently of Repeat A, and that protein-bridged interactions, not direct RNA contacts, underlie PRC recruitment by Airn, Xist, and other lncRNAs.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"70 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660409","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

Mind the gap: Intergenic regions in bacteria encode numerous small proteins 注意间隙：细菌的基因间区编码了许多小蛋白质

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.018

Jordan D. Lin, Ami S. Bhatt

引用次数: 0

A unified model for cohesin function in sisterchromatid cohesion and chromatin loop formation 姐妹染色单体内聚和染色质环形成中内聚功能的统一模型

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-20 DOI: 10.1016/j.molcel.2025.02.005

Frank Uhlmann

引用次数: 0

Base-pair resolution reveals clustered R-loops and DNA damage-susceptible R-loops 碱基对分辨率显示聚集的r -环和DNA损伤敏感的r -环

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-19 DOI: 10.1016/j.molcel.2025.02.019

Yaoyi Li, Yingliang Sheng, Chao Di, Hongjie Yao

{"title":"Base-pair resolution reveals clustered R-loops and DNA damage-susceptible R-loops","authors":"Yaoyi Li, Yingliang Sheng, Chao Di, Hongjie Yao","doi":"10.1016/j.molcel.2025.02.019","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.019","url":null,"abstract":"R-loops are pervasive triplex nucleic acid structures across diverse organisms, yet their biological functions remain incompletely understood. Here, we develop R-loop identification assisted by nucleases and sequencing (RIAN-seq), a nuclease-assisted, antibody-free sequencing technology, to map R-loops at base-pair resolution. By digesting single-stranded RNA (ssRNA), single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA) with nuclease P1, T5 exonuclease, and lambda exonuclease while preserving RNA:DNA hybrids, RIAN-seq achieves unprecedented precision in identifying the position and size of R-loops, detecting an order of magnitude more R-loops than existing methods. Approximately 50% of RNA:DNA hybrids span between 60 and 130 bp, with many forming previously undetectable clusters. Clustered R-loops at promoters recruit zinc-finger proteins VEZF1 and SP5, enhancing transcription in a number-dependent manner and resisting transcriptional perturbation. Conversely, R-loops featuring the Y(C/T)M(A/C)CAG motif at both ends contribute to DNA damage, a phenomenon conserved from yeast to mammalian cells. Our findings reveal a dual role for R-loops: clustered R-loops promote gene expression, while YMCAG-associated R-loops compromise genome stability.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"49 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653794","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

Biochemical profiling and structural basis of ADAR1-mediated RNA editing adar1介导的RNA编辑的生化分析和结构基础

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-17 DOI: 10.1016/j.molcel.2025.02.017

Xiangyu Deng, Lina Sun, Min Zhang, Rashmi Basavaraj, Jin Wang, Yi-Lan Weng, Yang Gao

{"title":"Biochemical profiling and structural basis of ADAR1-mediated RNA editing","authors":"Xiangyu Deng, Lina Sun, Min Zhang, Rashmi Basavaraj, Jin Wang, Yi-Lan Weng, Yang Gao","doi":"10.1016/j.molcel.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.017","url":null,"abstract":"ADAR1 regulates RNA-induced immune responses by converting adenosine to inosine in double-stranded RNA. Mutations in ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms underlying ADAR1-mediated editing remain unclear. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA-duplex-length dependent but can well tolerate mismatches near the editing site. High-resolution ADAR1-RNA complex structures, combined with mutagenesis, elucidate RNA binding, substrate selection, dimerization, and the essential role of RNA-binding domain 3. The ADAR1 structures also help explain the potential defects of disease-associated mutations, where biochemical and RNA sequencing analysis further indicate some of the mutations preferentially impact the editing of RNAs with short duplexes. These findings unveil the molecular basis of ADAR1 editing and provide insights into its immune-regulatory functions and therapeutic potential.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"69 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635583","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

Spatial control of m6A deposition on enhancer and promoter RNAs through co-acetylation of METTL3 and H3K27 on chromatin 通过染色质上METTL3和H3K27的共乙酰化调控m6A在增强子和启动子rna上的沉积

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-17 DOI: 10.1016/j.molcel.2025.02.016

Xiang Huang, Jie Zhang, Yixian Cun, Meijun Ye, Zhijun Ren, Wenbing Guo, Xiaojun Ma, Jiayin Liu, Weiwei Luo, Xiang Sun, Jingwen Shao, Zehong Wu, Xiaofeng Zhu, Jinkai Wang

{"title":"Spatial control of m6A deposition on enhancer and promoter RNAs through co-acetylation of METTL3 and H3K27 on chromatin","authors":"Xiang Huang, Jie Zhang, Yixian Cun, Meijun Ye, Zhijun Ren, Wenbing Guo, Xiaojun Ma, Jiayin Liu, Weiwei Luo, Xiang Sun, Jingwen Shao, Zehong Wu, Xiaofeng Zhu, Jinkai Wang","doi":"10.1016/j.molcel.2025.02.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.016","url":null,"abstract":"Interaction between the N6-methyladenosine (m6A) methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It remains to be uncovered whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR-Cas9 screening in the A549 cell line, we find that H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Consistently, p300 catalyzing the acetylation of METTL3 specifically occurs on H3K27ac-marked chromatin. Disruptive mutations on METTL3 acetylation sites selectively promote the m6A of chromatin-associated RNAs from p300-bound enhancers and promoters marked by H3K27ac, resulting in transcription inhibition of ferroptosis-inhibition-related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes ferroptosis in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"18 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635585","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

Profiling transcriptome composition and dynamics within nuclear compartments using SLAM-RT&Tag 利用SLAM-RT&Tag分析核室内转录组组成和动力学

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-11 DOI: 10.1016/j.molcel.2025.02.012

引用次数: 0