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 ~60% NAD + and NADH capping of yeast mitochondrial transcripts, and up to ~15% 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 transcriptional outputs, sensing NAD + and NADH levels and adjusting transcriptional outputs accordingly.
All Science Journal Classification (ASJC) codes
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)