Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase

Jeremy G. Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Atif Towheed, Douglas C. Wallace, Megerditch Kiledjian, Dmitry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere42179
JournaleLife
Volume7
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Bird, J. G., Basu, U., Kuster, D., Ramachandran, A., Grudzien-Nogalska, E., Towheed, A., Wallace, D. C., Kiledjian, M., Temiakov, D., Patel, S. S., Ebright, R. H., & Nickels, B. E. (2018). Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase eLife, 7, [e42179]. https://doi.org/10.7554/eLife.42179