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

Isioma I I Enwerem1, Nathan D Elrod2, Chung-Te Chang3

  • 1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.

RNA (New York, N.Y.)
|January 5, 2021
PubMed

Insights

Human Pumilio proteins (PUM1&2) control gene expression by degrading specific mRNAs. This study reveals PUM1&2 recruit the CCR4-NOT complex for mRNA decay, impacting vertebrate development and neurological functions.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Pumilio paralogs PUM1 and PUM2 are crucial RNA-binding proteins for vertebrate development and neurological functions.
  • PUM1&2 regulate gene expression by promoting the degradation of target messenger RNAs (mRNAs).

Purpose of the Study:

  • To elucidate the repression mechanism of human PUM1&2.
  • To determine the impact of PUM1&2 on the transcriptome.
  • To identify the molecular players involved in PUM1&2-mediated gene silencing.

Main Methods:

  • Interaction studies to identify protein partners of PUM1&2.
  • Isoform-level RNA sequencing to analyze transcriptome-wide effects.
  • Functional domain dissection of PUM1&2 proteins.

Main Results:

  • Subunits of the CCR4-NOT (CNOT) deadenylase complex are essential for PUM1&2 interaction and repression.
  • PUM1&2 directly recruit CNOT complex to target mRNAs, leading to their degradation.
  • A conserved N-terminal region of PUM1&2 mediates interaction with CNOT and confers repressive activity.
  • The mRNA decapping enzyme DCP2 plays a role in PUM1&2-mediated repression.

Conclusions:

  • Human PUM1&2 repress gene expression by directly recruiting the CNOT deadenylation complex.
  • This recruitment initiates a decapping-dependent mRNA decay pathway.
  • The findings provide a molecular model for PUM1&2 function in gene regulation.
Keywords:
CCR4-NOTPumiliodeadenylationmRNA decaytranslational repression

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