Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.037
Syed Nabeel-Shah, Shuye Pu, James D. Burns, Ulrich Braunschweig, Nujhat Ahmed, Giovanni L. Burke, Hyunmin Lee, Ernest Radovani, Guoqing Zhong, Hua Tang, Edyta Marcon, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt
{"title":"C2H2-zinc-finger transcription factors bind RNA and function in diverse post-transcriptional regulatory processes","authors":"Syed Nabeel-Shah, Shuye Pu, James D. Burns, Ulrich Braunschweig, Nujhat Ahmed, Giovanni L. Burke, Hyunmin Lee, Ernest Radovani, Guoqing Zhong, Hua Tang, Edyta Marcon, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt","doi":"10.1016/j.molcel.2024.08.037","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.037","url":null,"abstract":"<p>Cys2-His2 zinc-finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs) yet remain largely uncharacterized. Although certain family members, e.g., GTF3A, have been shown to bind both DNA and RNA, the extent to which C2H2-ZNFs interact with—and regulate—RNA-associated processes is not known. Using UV crosslinking and immunoprecipitation (CLIP), we observe that 148 of 150 analyzed C2H2-ZNFs bind directly to RNA in human cells. By integrating CLIP sequencing (CLIP-seq) RNA-binding maps for 50 of these C2H2-ZNFs with data from chromatin immunoprecipitation sequencing (ChIP-seq), protein-protein interaction assays, and transcriptome profiling experiments, we observe that the RNA-binding profiles of C2H2-ZNFs are generally distinct from their DNA-binding preferences and that they regulate a variety of post-transcriptional processes, including pre-mRNA splicing, cleavage and polyadenylation, and m<sup>6</sup>A modification of mRNA. Our results thus define a substantially expanded repertoire of C2H2-ZNFs that bind RNA and provide an important resource for elucidating post-transcriptional regulatory programs.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"5 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246010","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.029
Megan Palacio, Dylan J. Taatjes
{"title":"Transcription regulation through selective partitioning: Weak interactions with a strong foundation","authors":"Megan Palacio, Dylan J. Taatjes","doi":"10.1016/j.molcel.2024.08.029","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.029","url":null,"abstract":"<p>In this issue of <em>Molecular Cell</em>, De La Cruz, Pradhan, Veettil et al.<span><span><sup>1</sup></span></span> examine how selective partitioning of proteins via low-affinity IDR-dependent interactions may help regulate RNA polymerase II (RNA Pol II) function and identify sequence features that drive partitioning in cells.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"332 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246011","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.010
Maya L. Gosztyla, Lijun Zhan, Sara Olson, Xintao Wei, Jack Naritomi, Grady Nguyen, Lena Street, Grant A. Goda, Francisco F. Cavazos, Jonathan C. Schmok, Manya Jain, Easin Uddin Syed, Eunjeong Kwon, Wenhao Jin, Eric Kofman, Alexandra T. Tankka, Allison Li, Valerie Gonzalez, Eric Lécuyer, Daniel Dominguez, Gene W. Yeo
{"title":"Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation","authors":"Maya L. Gosztyla, Lijun Zhan, Sara Olson, Xintao Wei, Jack Naritomi, Grady Nguyen, Lena Street, Grant A. Goda, Francisco F. Cavazos, Jonathan C. Schmok, Manya Jain, Easin Uddin Syed, Eunjeong Kwon, Wenhao Jin, Eric Kofman, Alexandra T. Tankka, Allison Li, Valerie Gonzalez, Eric Lécuyer, Daniel Dominguez, Gene W. Yeo","doi":"10.1016/j.molcel.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.010","url":null,"abstract":"<p>RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation. The examined ZFPs show widespread sequence-specific RNA binding and preferentially bind proximal to transcription start sites. Additionally, several ZFPs associate with their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DNA/RNA-associated protein that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"13 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246241","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.034
Jonathan N. Pruneda, Felix Randow
{"title":"Ubiquitylation: Sword and shield in the bacterial arsenal","authors":"Jonathan N. Pruneda, Felix Randow","doi":"10.1016/j.molcel.2024.08.034","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.034","url":null,"abstract":"<p>In two recent studies in <em>Nature</em>, Hör et al.<span><span><sup>1</sup></span></span> and Chambers et al.<span><span><sup>2</sup></span></span> report that ubiquitin-like conjugation in bacteria antagonizes phage replication.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"26 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246057","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.031
Hongxin Yin, Yang Liu
{"title":"Finish the unfinished: Chd1 resolving hexasome-nucleosome complex with FACT","authors":"Hongxin Yin, Yang Liu","doi":"10.1016/j.molcel.2024.08.031","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.031","url":null,"abstract":"<p>In this issue of <em>Molecular Cell</em>, Engeholm et al.<span><span><sup>1</sup></span></span> present cryo-EM structures of the chromatin remodeler Chd1 bound to a hexasome-nucleosome complex, an intermediate state during transcription either with or without FACT to restore the missing H2A-H2B dimer. These two binding modes reveal how Chd1 and FACT cooperate in nucleosome re-establishment during transcription.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"483 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246067","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.033
Teppei Morita, Susan Gottesman
{"title":"Coming in out of the cold: Rho-dependent termination contributes to adaptation to cold shock","authors":"Teppei Morita, Susan Gottesman","doi":"10.1016/j.molcel.2024.08.033","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.033","url":null,"abstract":"<p>During cold shock, bacteria shut down translation of all but a set of cold-shock proteins critical for recovery; in this issue of <em>Molecular Cell</em>, Delaleau et al.<span><span><sup>1</sup></span></span> show that Rho-dependent transcription termination plays an important role in cold adaptation, via temperature-regulated termination of the cold-shock protein mRNAs.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"5 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246126","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}
Molecular CellPub Date : 2024-09-19DOI: 10.1016/j.molcel.2024.08.026
Bo Lv, William A. Dion, Haoxiang Yang, Jinrui Xun, Do-Hyung Kim, Bokai Zhu, Jay Xiaojun Tan
{"title":"A TBK1-independent primordial function of STING in lysosomal biogenesis","authors":"Bo Lv, William A. Dion, Haoxiang Yang, Jinrui Xun, Do-Hyung Kim, Bokai Zhu, Jay Xiaojun Tan","doi":"10.1016/j.molcel.2024.08.026","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.026","url":null,"abstract":"<p>Stimulator of interferon genes (STING) is activated in many pathophysiological conditions, leading to TBK1-dependent interferon production in higher organisms. However, primordial functions of STING independent of TBK1 are poorly understood. Here, through proteomics and bioinformatics approaches, we identify lysosomal biogenesis as an unexpected function of STING. Transcription factor EB (TFEB), an evolutionarily conserved regulator of lysosomal biogenesis and host defense, is activated by STING from multiple species, including humans, mice, and frogs. STING-mediated TFEB activation is independent of TBK1, but it requires STING trafficking and its conserved proton channel. GABARAP lipidation, stimulated by the channel of STING, is key for STING-dependent TFEB activation. STING stimulates global upregulation of TFEB-target genes, mediating lysosomal biogenesis and autophagy. TFEB supports cell survival during chronic sterile STING activation, a common condition in aging and age-related diseases. These results reveal a primordial function of STING in the biogenesis of lysosomes, essential organelles in immunity and cellular stress resistance.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"195 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246009","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}
Molecular CellPub Date : 2024-09-12DOI: 10.1016/j.molcel.2024.08.002
Jingyi Ren, Shuchen Luo, Hailing Shi, Xiao Wang
{"title":"Spatial omics advances for in situ RNA biology","authors":"Jingyi Ren, Shuchen Luo, Hailing Shi, Xiao Wang","doi":"10.1016/j.molcel.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.002","url":null,"abstract":"<p>Spatial regulation of RNA plays a critical role in gene expression regulation and cellular function. Understanding spatially resolved RNA dynamics and translation is vital for bringing new insights into biological processes such as embryonic development, neurobiology, and disease pathology. This review explores past studies in subcellular, cellular, and tissue-level spatial RNA biology driven by diverse methodologies, ranging from cell fractionation, <em>in situ</em> and proximity labeling, imaging, spatially indexed next-generation sequencing (NGS) approaches, and spatially informed computational modeling. Particularly, recent advances have been made for near-genome-scale profiling of RNA and multimodal biomolecules at high spatial resolution. These methods enabled new discoveries into RNA’s spatiotemporal kinetics, RNA processing, translation status, and RNA-protein interactions in cells and tissues. The evolving landscape of experimental and computational strategies reveals the complexity and heterogeneity of spatial RNA biology with subcellular resolution, heralding new avenues for RNA biology research.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"104 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171419","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}
Molecular CellPub Date : 2024-09-12DOI: 10.1016/j.molcel.2024.08.022
Maik Engeholm, Johann J. Roske, Elisa Oberbeckmann, Christian Dienemann, Michael Lidschreiber, Patrick Cramer, Lucas Farnung
{"title":"Resolution of transcription-induced hexasome-nucleosome complexes by Chd1 and FACT","authors":"Maik Engeholm, Johann J. Roske, Elisa Oberbeckmann, Christian Dienemann, Michael Lidschreiber, Patrick Cramer, Lucas Farnung","doi":"10.1016/j.molcel.2024.08.022","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.022","url":null,"abstract":"<p>To maintain the nucleosome organization of transcribed genes, ATP-dependent chromatin remodelers collaborate with histone chaperones. Here, we show that at the 5′ ends of yeast genes, RNA polymerase II (RNAPII) generates hexasomes that occur directly adjacent to nucleosomes. The resulting hexasome-nucleosome complexes are then resolved by Chd1. We present two cryoelectron microscopy (cryo-EM) structures of Chd1 bound to a hexasome-nucleosome complex before and after restoration of the missing inner H2A/H2B dimer by FACT. Chd1 uniquely interacts with the complex, positioning its ATPase domain to shift the hexasome away from the nucleosome. In the absence of the inner H2A/H2B dimer, its DNA-binding domain (DBD) packs against the ATPase domain, suggesting an inhibited state. Restoration of the dimer by FACT triggers a rearrangement that displaces the DBD and stimulates Chd1 remodeling. Our results demonstrate how chromatin remodelers interact with a complex nucleosome assembly and suggest how Chd1 and FACT jointly support transcription by RNAPII.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"41 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171418","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}
Molecular CellPub Date : 2024-09-10DOI: 10.1016/j.molcel.2024.08.023
Teodorus Theo Susanto, Victoria Hung, Andrew G. Levine, Yuxiang Chen, Craig H. Kerr, Yongjin Yoo, Juan A. Oses-Prieto, Lisa Fromm, Zijian Zhang, Travis C. Lantz, Kotaro Fujii, Marius Wernig, Alma L. Burlingame, Davide Ruggero, Maria Barna
{"title":"RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages","authors":"Teodorus Theo Susanto, Victoria Hung, Andrew G. Levine, Yuxiang Chen, Craig H. Kerr, Yongjin Yoo, Juan A. Oses-Prieto, Lisa Fromm, Zijian Zhang, Travis C. Lantz, Kotaro Fujii, Marius Wernig, Alma L. Burlingame, Davide Ruggero, Maria Barna","doi":"10.1016/j.molcel.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.023","url":null,"abstract":"<p>Ribosomes are emerging as direct regulators of gene expression, with ribosome-associated proteins (RAPs) allowing ribosomes to modulate translation. Nevertheless, a lack of technologies to enrich RAPs across sample types has prevented systematic analysis of RAP identities, dynamics, and functions. We have developed a label-free methodology called RAPIDASH to enrich ribosomes and RAPs from any sample. We applied RAPIDASH to mouse embryonic tissues and identified hundreds of potential RAPs, including Dhx30 and Llph, two forebrain RAPs important for neurodevelopment. We identified a critical role of LLPH in neural development linked to the translation of genes with long coding sequences. In addition, we showed that RAPIDASH can identify ribosome changes in cancer cells. Finally, we characterized ribosome composition remodeling during immune cell activation and observed extensive changes post-stimulation. RAPIDASH has therefore enabled the discovery of RAPs in multiple cell types, tissues, and stimuli and is adaptable to characterize ribosome remodeling in several contexts.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"103 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160994","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}