Pentatricopeptide Repeat Poly(A) Binding Protein KPAF4 Stabilizes Mitochondrial MRNAs in Trypanosoma Brucei

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jan 13

PMID 30635574

Citations 11

Authors

Mikhail V Mesitov

Tian Yu

Takuma Suematsu

Francois M Sement

Liye Zhang

Clinton Yu

Lan Huang

Inna Aphasizheva

Affiliations

Soon will be listed here.

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.

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