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Pentatricopeptide repeat poly(A) binding protein KPAF4 stabilizes mitochondrial mRNAs in Trypanosoma brucei

Mikhail V Mesitov1, Tian Yu1,2, Takuma Suematsu1

  • 1Department of Molecular and Cell Biology, Boston University Medical Campus, Boston, MA, 02118, USA.

Nature Communications
|January 13, 2019
PubMed

Insights

Researchers identified KPAF4, a poly(A) binding protein, that regulates mRNA processing in Trypanosoma brucei. KPAF4 ensures proper RNA editing and 3' modification, preventing premature translation of incompletely edited mRNAs.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Parasitology

Background:

  • Mitochondrial mRNA processing in Trypanosoma brucei involves editing and 3' modifications.
  • Poly(A) binding proteins (PABP) are implicated in coordinating these processes, but their specific roles and identities were unknown.

Purpose of the Study:

  • To identify the PABP involved in coordinating mRNA editing and 3' modification in Trypanosoma brucei.
  • To elucidate the mechanism by which this PABP regulates mRNA processing and translation.

Main Methods:

  • Protein identification and characterization (KPAF4).
  • Analysis of mRNA 3' end modifications (adenylation and uridylation).
  • Investigation of protein-RNA interactions and mRNA circularization via RESC complex.

Main Results:

  • Identified KPAF4, a pentatricopeptide repeat-containing PABP, that binds to the A-tail of mRNAs.
  • KPAF4 prevents premature mRNA degradation and inhibits uridylation of partially edited transcripts, acting as a quality control mechanism.
  • RESC complex mediates interaction between MERS1 and KPAF4, facilitating mRNA circularization crucial for stability.

Conclusions:

  • KPAF4 plays a critical role in regulating mRNA editing and 3' end processing in Trypanosoma brucei.
  • The KPAF4-mediated quality control prevents translation of incompletely edited mRNAs.
  • mRNA circularization involving KPAF4 and MERS1 is essential for edited mRNA stability.

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