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

2 Citations (Scopus)

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

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DNA-Directed RNA Polymerases
NAD
Yeast
Yeasts
RNA Caps
Nuclear RNA
mitochondrial RNA
RNA
Transcription Initiation Site
Transcription
Metabolism

All Science Journal Classification (ASJC) codes

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

Cite this

Bird, J. G., Basu, U., Kuster, D., Ramachandran, A., Grudzien-Nogalska, E., Towheed, A., ... 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
Bird, Jeremy G. ; Basu, Urmimala ; Kuster, David ; Ramachandran, Aparna ; Grudzien-Nogalska, Ewa ; Towheed, Atif ; Wallace, Douglas C. ; Kiledjian, Megerditch ; Temiakov, Dmitry ; Patel, Smita S. ; Ebright, Richard H. ; Nickels, Bryce E. / Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase In: eLife. 2018 ; Vol. 7.
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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, Ebright, RH & Nickels, BE 2018, ' Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase ', eLife, vol. 7, e42179. https://doi.org/10.7554/eLife.42179

Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase . / Bird, Jeremy G.; Basu, Urmimala; Kuster, David; Ramachandran, Aparna; Grudzien-Nogalska, Ewa; Towheed, Atif; Wallace, Douglas C.; Kiledjian, Megerditch; Temiakov, Dmitry; Patel, Smita S.; Ebright, Richard H.; Nickels, Bryce E.

In: eLife, Vol. 7, e42179, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - Highly efficient 5’ capping of mitochondrial RNA with nad + and NADH by yeast and human mitochondrial RNA polymerase

AU - Bird, Jeremy G.

AU - Basu, Urmimala

AU - Kuster, David

AU - Ramachandran, Aparna

AU - Grudzien-Nogalska, Ewa

AU - Towheed, Atif

AU - Wallace, Douglas C.

AU - Kiledjian, Megerditch

AU - Temiakov, Dmitry

AU - Patel, Smita S.

AU - Ebright, Richard H.

AU - Nickels, Bryce E.

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AB - 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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