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PABP Cooperates with the CCR4-NOT Complex to Promote mRNA Deadenylation and Block Precocious Decay

Hyerim Yi1, Joha Park1, Minju Ha1

  • 1Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.

Molecular Cell
|June 23, 2018
PubMed

Insights

The CCR4-NOT (CNOT) complex is a major deadenylase for cytoplasmic RNAs. Poly(A) binding protein (PABP) aids deadenylation, preventing premature decay and uridylation.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Biochemistry

Background:

  • Vertebrates possess multiple deadenylases: PAN2-PAN3 (PAN2/3), CCR4-NOT (CNOT), and PARN.
  • The specific roles of these deadenylases and poly(A) binding protein (PABP) in mRNA deadenylation are not fully understood.

Purpose of the Study:

  • To elucidate the distinct functions of deadenylase complexes (CNOT, PAN2/3, PARN) in mRNA deadenylation.
  • To clarify the role of PABP in the deadenylation process and its interplay with deadenylases.

Main Methods:

  • Investigated deadenylation activities of CNOT, PAN2/3, and PARN complexes in vitro.
  • Analyzed the impact of PABP on deadenylation by CAF1 and CCR4 subunits.
  • Characterized the trimming of poly(A) tails by different deadenylases.

Main Results:

  • CNOT acts as a predominant nonspecific deadenylase for cytoplasmic poly(A)+ RNAs.
  • PABP promotes deadenylation and prevents premature uridylation and decay.
  • PAN2/3 selectively trims long poly(A) tails (>150 nt) with limited transcriptome-wide impact.
  • PARN does not significantly affect mRNA deadenylation.
  • CAF1 trims naked poly(A) tails, inhibited by PABP; CCR4 is activated by PABP.
  • CAF1 and CCR4 actions define PABP footprints on shortening poly(A) tails.

Conclusions:

  • Distinct roles of deadenylases (CNOT, PAN2/3, PARN) and PABP in mRNA deadenylation are revealed.
  • The interplay between PABP and CNOT subunits (CAF1, CCR4) dictates poly(A) tail shortening dynamics.
  • This study redefines the understanding of mRNA deadenylation mechanisms and regulation.
Keywords:
CAF1CCR4CCR4-NOTPABPCPAN2-PAN3PARNRNA decaydeadenylationpoly(A) tailuridylation

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