Mitochondrial RNA capping: highly efficient 5'-RNA capping with NAD+and NADH by yeast and human mitochondrial RNA polymerase [article]

Jeremy G. Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Megerditch Kiledjian, Dimtry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels
2018 bioRxiv   pre-print
Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+and NADH, using NAD+and NADH as non canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to
more » ... 50% NAD+and ~40% NADH capping of yeast mitochondrial transcripts, and up to ~10% NAD+capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at and upstream of the transcription start site and, in yeast and human cells, by intracellular NAD+and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial gene expression, sensing NAD+and NADH levels and adjusting transcriptional outputs accordingly.
doi:10.1101/381160 fatcat:ck3mnjdmvvfqjimqcfuc5zsku4