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

被引:36
|
作者
Enwerem, Isioma I. I. [1 ,5 ]
Elrod, Nathan D. [2 ]
Chang, Chung-Te [3 ,6 ]
Lin, Ai [2 ]
Ji, Ping [2 ]
Bohn, Jennifer A. [4 ,7 ]
Levdansky, Yevgen [3 ,8 ]
Wagner, Eric J. [2 ]
Valkov, Eugene [3 ,8 ]
Goldstrohm, Aaron C. [1 ,4 ]
机构
[1] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA
[2] Univ Texas Med Branch Galveston, Dept Biochem & Mol Biol, Galveston, TX 77550 USA
[3] Max Planck Inst Dev Biol, Dept Biochem, D-72076 Tubingen, Germany
[4] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
[5] Emory Univ, Dept Biochem Engn, Atlanta, GA 30322 USA
[6] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 11221, Taiwan
[7] Rockefeller Univ, Lab Retrovirol, New York, NY 10065 USA
[8] NCI, Messenger RNA Regulat & Decay Sect, RNA Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA
基金
美国国家卫生研究院;
关键词
Pumilio; CCR4-NOT; deadenylation; translational repression; mRNA decay; MESSENGER-RNA DEGRADATION; TETHERED FUNCTION ASSAYS; LONG NONCODING RNAS; TRANSLATIONAL REPRESSION; DIRECTLY RECRUITS; DECAPPING ENZYME; STRUCTURAL BASIS; NANOS; RECOGNITION; INSIGHTS;
D O I
10.1261/rna.078436.120
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:445 / 464
页数:20
相关论文
共 50 条
  • [1] Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex
    Haugen, Rebecca J.
    Barnier, Catherine
    Elrod, Nathan D.
    Luo, Hua
    Jensen, Madeline K.
    Ji, Ping
    Smibert, Craig A.
    Lipshitz, Howard D.
    Wagner, Eric J.
    Freddolino, P. Lydia
    Goldstrohm, Aaron C.
    RNA, 2024, 30 (07) : 866 - 890
  • [2] The CCR4-NOT Deadenylase Complex Maintains Adipocyte Identity
    Takahashi, Akinori
    Takaoka, Shohei
    Kobori, Shungo
    Yamaguchi, Tomokazu
    Ferwati, Sara
    Kuba, Keiji
    Yamamoto, Tadashi
    Suzuki, Toru
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (21)
  • [3] Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin
    Fabian, Marc R.
    Frank, Filipp
    Rouya, Christopher
    Siddiqui, Nadeem
    Lai, Wi S.
    Karetnikov, Alexey
    Blackshear, Perry J.
    Nagar, Bhushan
    Sonenberg, Nahum
    NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (06) : 735 - +
  • [4] HIPK family kinases bind and regulate the function of the CCR4-NOT complex
    Rodriguez-Gil, Alfonso
    Ritter, Olesja
    Hornung, Juliane
    Stekman, Hilda
    Krueger, Marcus
    Braun, Thomas
    Kremmer, Elisabeth
    Kracht, Michael
    Schmitz, M. Lienhard
    MOLECULAR BIOLOGY OF THE CELL, 2016, 27 (12) : 1969 - 1980
  • [5] Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex
    Miyasaka, Takashi
    Morita, Masahiro
    Ito, Kentaro
    Suzuki, Toru
    Fukuda, Hiroyuki
    Takeda, Shizu
    Inoue, Jun-Ichiro
    Semba, Kentaro
    Yamamoto, Tadashi
    CANCER SCIENCE, 2008, 99 (04) : 755 - 761
  • [6] Involvement of the CCR4-NOT Deadenylase Complex in the Control of Cell Growth
    Morita, Masahiro
    Ito, Kentaro
    Suzuki, Toru
    Yamamoto, Tadashi
    SYSTEMS BIOLOGY: THE CHALLENGE OF COMPLEXITY, 2009, : 229 - +
  • [7] Human Ccr4-Not complexes contain variable deadenylase subunits
    Lau, Nga-Chi
    Kolkman, Annemieke
    van Schaik, Frederik M. A.
    Mulder, Klaas W.
    Pijnappel, W. W. M. Pim
    Heck, Albert J. R.
    Timmers, H. Th. Marc
    BIOCHEMICAL JOURNAL, 2009, 422 : 443 - 453
  • [8] Ccr4-Not complex directly regulates transcription elongation
    Reese, Joseph C.
    Kruk, Jennifer A.
    Dutta, Arnob
    Gilmour, David S.
    FASEB JOURNAL, 2010, 24
  • [9] Novel interaction between CCR4 and CAF1 in rice CCR4-NOT deadenylase complex
    Chou, Wei-Lun
    Chung, Yue-Lin
    Fang, Jhen-Cheng
    Lu, Chung-An
    PLANT MOLECULAR BIOLOGY, 2017, 93 (1-2) : 79 - 96
  • [10] A conserved domain of Drosophila RNA-binding protein Pumilio interacts with multiple CCR4-NOT deadenylase complex subunits to repress target mRNAs
    Haugen, Rebecca J.
    Arvola, Rene M.
    Connacher, Robert P.
    Roden, Richard T.
    Goldstrohm, Aaron C.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2022, 298 (09)