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Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome

  1. Author:
    Enwerem, Isioma I. I.
    Elrod, Nathan D.
    Chang, Chung-Te
    Lin, Ai
    Ji, Ping
    Bohn, Jennifer A.
    Levdansky,Yevgen
    Wagner, Eric J.
    Valkov,Eugene
    Goldstrohm, Aaron C.

  2. Author Address

    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.Univ Texas Med Branch Galveston, Dept Biochem & Mol Biol, Galveston, TX 77550 USA.Max Planck Inst Dev Biol, Dept Biochem, D-72076 Tubingen, Germany.Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.Emory Univ, Dept Biochem Engn, Atlanta, GA 30322 USA.Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 11221, Taiwan.Rockefeller Univ, Lab Retrovirol, New York, NY 10065 USA.NCI, Messenger RNA Regulat & Decay Sect, RNA Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
    1. Year: 2021
    2. Date: Apr
  2. Journal: RNA
  3. Cold Spring Harbor Lab Press, Publications Dept
    1. 27
    2. 4
    3. Pages: 445-464
  5. Type of Article: Article
  6. ISSN: 1355-8382
  1. Abstract:

    Pumilio paralogs, PUM1 and PUM2, are sequence-specific RNA-binding proteins that are essential for vertebrate development and neurological functions. PUM1&2 negatively regulate gene expression by accelerating degradation of specific mRNAs. Here, we determined the repression mechanism and impact of human PUM1&2 on the transcriptome. We identified subunits of the CCR4-NOT (CNOT) deadenylase complex required for stable interaction with PUM1&2 and to elicit CNOT-dependent repression. Isoform-level RNA sequencing revealed broad coregulation of target mRNAs through the PUM-CNOT repression mechanism. Functional dissection of the domains of PUM1&2 identified a conserved amino-terminal region that confers the predominant repressive activity via direct interaction with CNOT. In addition, we show that the mRNA decapping enzyme, DCP2, has an important role in repression by PUM1&2 amino-terminal regions. Our results support a molecular model of repression by human PUM1&2 via direct recruitment of CNOT deadenylation machinery in a decapping-dependent mRNA decay pathway.

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External Sources

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  2. DOI: 10.1261/rna.078436.120
  3. View record in Web of Science®
  4. WOS: 000629533500008

Library Notes

  1. Fiscal Year: FY2020-2021
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