Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Oct 8

PMID 31588022

Citations 14

Authors

Thomas J Nicholls

Henrik Spahr

Shan Jiang

Stefan J Siira

Camilla Koolmeister

Sushma Sharma

Johanna H K Kauppila

Min Jiang

Volkhard Kaever

Oliver Rackham

Andrei Chabes

Maria Falkenberg

Aleksandra Filipovska

Nils-Goran Larsson

Claes M Gustafsson

Affiliations

Soon will be listed here.

Abstract

Oligoribonucleases are conserved enzymes that degrade short RNA molecules of up to 5 nt in length and are assumed to constitute the final stage of RNA turnover. Here we demonstrate that REXO2 is a specialized dinucleotide-degrading enzyme that shows no preference between RNA and DNA dinucleotide substrates. A heart- and skeletal-muscle-specific knockout mouse displays elevated dinucleotide levels and alterations in gene expression patterns indicative of aberrant dinucleotide-primed transcription initiation. We find that dinucleotides act as potent stimulators of mitochondrial transcription initiation in vitro. Our data demonstrate that increased levels of dinucleotides can be used to initiate transcription, leading to an increase in transcription levels from both mitochondrial promoters and other, nonspecific sequence elements in mitochondrial DNA. Efficient RNA turnover by REXO2 is thus required to maintain promoter specificity and proper regulation of transcription in mammalian mitochondria.

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