Inna Afasizheva, PhD
|Institution||Boston University Henry M. Goldman School of Dental Medicine|
|Department||Molecular & Cell Biology|
mitochondrial gene expression
Regulation of Mitochondrial Gene Expression by Pentatricopeptide Repeat RNA Binding Proteins -
The majority of trypanosomal mitochondrial pre-mRNAs undergo massive uridine insertion/deletion editing which creates open reading frames. However, our recent findings indicated that pre- and post-editing processing steps are also required to produce translation-competent mRNAs. Pre-editing addition of short 3' A-tails exerts no influence on unedited pre-mRNA stability, but stabilizes transcripts that are edited beyond few initial sites. The post-editing extension of A-tails into A/U heteropolymers by KPAP1 poly(A) polymerase and RET1 TUTase commits fully-edited mRNAs to translation. To identify factors responsible for coupling of editing, polyadenylation, and translation, we built a comprehensive protein interactions network of respective machineries. The ensuing RNAi screen distinguished several pentatricopeptide repeat-containing (PPR) RNA binding proteins acting to: 1) stabilize mRNA prior to polyadenylation 2) block premature mRNA uridylation and 3) induce transcript-specific adenylation uridylation.
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