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Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals

  1. Author:
    Lee, Seungjae
    Jee, David
    Srivastava, Sid
    Yang,Acong
    Ramidi, Abhinav
    Shang, Renfu
    Bortolamiol-Becet, Diane
    Pfeffer, Sébastien
    Gu,Shuo
    Wen, Jiayu
    Lai, Eric C

  2. Author Address

    1Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA. 2Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Weill Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065, USA. 3Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; High Technology High School, Lincroft, NJ 07738, USA. 4RNA Biology Laboratory, Center for Cancer Research, 8 National Cancer Institute, Frederick, MD 21702, USA. 5Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Université de Strasbourg, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, 2 Allée Konrad Roentgen, 67084 Strasbourg, France. 6Université de Strasbourg, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, 2 Allée Konrad Roentgen, 67084 Strasbourg, France. 7Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia. Electronic address: jiayu.wen@anu.edu.au. 8Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Weill Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: laie@mskcc.org.
    1. Year: 2023
    2. Date: Feb 16
    3. Epub Date: 2023 02 16
  2. Journal: Cell Reports
    1. 42
    2. 2
    3. Pages: 112111
  4. Type of Article: Article
  5. Article Number: 112111
  1. Abstract:

    Canonical microRNA (miRNA) hairpins are processed by the RNase III enzymes Drosha and Dicer into ~22 nt RNAs loaded into an Argonaute (Ago) effector. In addition, splicing generates numerous intronic hairpins that bypass Drosha (mirtrons) to yield mature miRNAs. Here, we identify hundreds of previously unannotated, splicing-derived hairpins in intermediate-length (~50-100 nt) but not small (20-30 nt) RNA data. Since we originally defined mirtrons from small RNA duplexes, we term this larger set as structured splicing-derived RNAs (ssdRNAs). These associate with Dicer and/or Ago complexes, but generally accumulate modestly and are poorly conserved. We propose they contaminate the canonical miRNA pathway, which consequently requires defense against the siege of splicing-derived substrates. Accordingly, ssdRNAs/mirtrons comprise dominant hairpin substrates for 3' tailing by multiple terminal nucleotidyltransferases, notably TUT4/7 and TENT2. Overall, the rampant proliferation of young mammalian mirtrons/ssdRNAs, coupled with an inhibitory molecular defense, comprises a Red Queen's race of intragenomic conflict. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.celrep.2023.112111
  3. PMID: 36800291
  4. PII : S2211-1247(23)00122-5

Library Notes

  1. Fiscal Year: FY2022-2023
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