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.

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Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S.

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Bird JG, Basu U, Kuster D, Ramachandran A, Grudzien-Nogalska E, Towheed A, Wallace DC, Kiledjian M, Temiakov D, Patel SS, ... Show all

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