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Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.
Gosztyla, Maya L; Zhan, Lijun; Olson, Sara; Wei, Xintao; Naritomi, Jack; Nguyen, Grady; Street, Lena; Goda, Grant A; Cavazos, Francisco F; Schmok, Jonathan C; Jain, Manya; Uddin Syed, Easin; Kwon, Eunjeong; Jin, Wenhao; Kofman, Eric; Tankka, Alexandra T; Li, Allison; Gonzalez, Valerie; Lécuyer, Eric; Dominguez, Daniel; Jovanovic, Marko; Graveley, Brenton R; Yeo, Gene W.
  • Gosztyla ML; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Zhan L; Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT 06030, USA.
  • Olson S; Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT 06030, USA.
  • Wei X; Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT 06030, USA.
  • Naritomi J; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Nguyen G; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Street L; Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
  • Goda GA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Cavazos FF; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Schmok JC; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Jain M; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Uddin Syed E; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada; School of Pharmacy, Brac University, Dhaka 1212, Bangladesh.
  • Kwon E; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.
  • Jin W; Sanford Laboratories for Innovative Medicines, La Jolla, CA 92037, USA.
  • Kofman E; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Tankka AT; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Li A; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Gonzalez V; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
  • Lécuyer E; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada; Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada.
  • Dominguez D; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Jovanovic M; Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
  • Graveley BR; Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT 06030, USA.
  • Yeo GW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA; Sanford Stem Cell Institute and UCSD Stem Cell Program, University of California San Diego, La Jolla, CA 92037, USA; Institute for Genomic Medicine, University of California, San Diego, La Jol
Mol Cell ; 2024 Sep 16.
Article en En | MEDLINE | ID: mdl-39303722
ABSTRACT
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.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article