Pluto Bioinformatics

GSE129707: Dinucleotide regulation by REXO2 maintains promoter specificity in mammalian mitochondria

Bulk RNA sequencing

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. We have investigated the function of the mammalian oligoribonuclease REXO2 through a combination of biochemical, structural and animal model studies. We find that REXO2 is a specialised dinucleotide degrading enzyme that shows no preference between RNA and DNA dinucleotide substrates. This specialisation is explained by crystal structures of REXO2 bound to RNA or DNA substrates. REXO2 is an essential gene, while 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, and conclude that efficient RNA turnover is required to maintain the promoter specificity of transcription in mammalian mitochondria. SOURCE: Stefan,J,SiiraMitochondrial medicine and biology Harry Perkins Institute of Medical Research