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

Nat Commun. 2019 Jan 11;10(1):146. doi: 10.1038/s41467-018-08137-2.

Abstract

In Trypanosoma brucei, most mitochondrial mRNAs undergo editing, and 3' adenylation and uridylation. The internal sequence changes and terminal extensions are coordinated: pre-editing addition of the short (A) tail protects the edited transcript against 3'-5' degradation, while post-editing A/U-tailing renders mRNA competent for translation. Participation of a poly(A) binding protein (PABP) in coupling of editing and 3' modification processes has been inferred, but its identity and mechanism of action remained elusive. We report identification of KPAF4, a pentatricopeptide repeat-containing PABP which sequesters the A-tail and impedes mRNA degradation. Conversely, KPAF4 inhibits uridylation of A-tailed transcripts and, therefore, premature A/U-tailing of partially-edited mRNAs. This quality check point likely prevents translation of incompletely edited mRNAs. We also find that RNA editing substrate binding complex (RESC) mediates the interaction between the 5' end-bound pyrophosphohydrolase MERS1 and 3' end-associated KPAF4 to enable mRNA circularization. This event appears to be critical for edited mRNA stability.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Mitochondria / genetics
  • Poly(A)-Binding Proteins / metabolism*
  • RNA Editing / genetics*
  • RNA Interference
  • RNA Stability / genetics*
  • RNA, Messenger / genetics*
  • RNA, Mitochondrial / genetics*
  • RNA, Protozoan / genetics*
  • RNA, Small Interfering / genetics
  • Trypanosoma brucei brucei / genetics*

Substances

  • Poly(A)-Binding Proteins
  • RNA, Messenger
  • RNA, Mitochondrial
  • RNA, Protozoan
  • RNA, Small Interfering
  • mitochondrial messenger RNA