SUV3 helicase is required for correct processing of mitochondrial transcripts.

Paula Clemente,Anna Wredenberg,Isabelle Laine,Aleksandra Pajak,Rolf Wibom,Christoph Freyer,Anna Wedell

doi:10.1093/nar/gkv692

Abstract

Mitochondrial gene expression is largely regulated by post-transcriptional mechanisms that control the amount and translation of each mitochondrial mRNA. Despite its importance for mitochondrial function, the mechanisms and proteins involved in mRNA turnover are still not fully characterized. Studies in yeast and human cell lines have indicated that the mitochondrial helicase SUV3, together with the polynucleotide phosphorylase, PNPase, composes the mitochondrial degradosome. To further investigate the in vivo function of SUV3 we disrupted the homolog of SUV3 in Drosophila melanogaster (Dm). Loss of dmsuv3 led to the accumulation of mitochondrial mRNAs, without increasing rRNA levels, de novo transcription or decay intermediates. Furthermore, we observed a severe decrease in mitochondrial tRNAs accompanied by an accumulation of unprocessed precursor transcripts. These processing defects lead to reduced mitochondrial translation and a severe respiratory chain complex deficiency, resulting in a pupal lethal phenotype. In summary, our results propose that SUV3 is predominantly required for the processing of mitochondrial polycistronic transcripts in metazoan and that this function is independent of PNPase.

Highlights

All cellular systems require a variety of regulatory mechanisms to remove redundant or incorrect RNAs
Drosophila melanogaster (Dm) has been proven as an excellent model system to study post-transcriptional regulation mechanisms in vivo, with many factors involved in mitochondrial gene expression conserved between Dm and humans
Mitochondrial targeting prediction suggests that DmSUV3 is a mitochondrial protein using either Mitoprot II (0.969) or Target P (0.946) software

Summary

Introduction

All cellular systems require a variety of regulatory mechanisms to remove redundant or incorrect RNAs. clearly defined for cytosolic RNAs into different decay pathways, mitochondrial RNA degradation is more elusive with several protein complexes proposed to function as mitochondrial degradosomes [1]. A range of different RNAs species, including mRNAs, rRNAs and tRNAs, as well as a variety of non-coding RNAs and antisense RNAs, are generated and a putative degradation machinery has to distinguish between them, to ensure controlled gene expression. Polyadenylation has been proposed to be required for correct translation of the majority of transcripts [11], not all mitochondrial mRNAs are polyadenylated and polyadenylation-like signals have even been observed as part of the degradation pathway [12]. Characterization of the mitochondrial degradosomes might shed light on mechanisms regulating mitochondrial RNA stability

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