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Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

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

in Adenine / Adenosine / Biochemistry / Biochemistry and Chemical Biology / Chromosomes and Gene Expression / Cytoplasm - genetics / Cytoplasm - metabolism / Deoxyribonucleic acid / DNA / DNA-directed RNA polymerase / DNA-Directed RNA Polymerases - genetics / Humans / metabolism / Mitochondria / Mitochondria - genetics / Molecular biology / NAD / NAD - genetics / NADH / Nicotinamide / non-canonical initiating nucleotide / Nucleotides / Oxidation-Reduction / Promoter Regions, Genetic / Proteins / Quantitation / RNA capping / RNA Caps - genetics / RNA polymerase / RNA, Mitochondrial - genetics / Saccharomyces cerevisiae - genetics / Transcription initiation / Transcription Initiation Site / Transcription, Genetic / Yeast

2018

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Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

2018

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Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

2018

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Journal Article

Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

Grudzien-Nogalska, Ewa,

Kiledjian, Megerditch,

Temiakov, Dmitry,

Patel, Smita S,

Wallace, Douglas C,

Towheed, Atif,

Kuster, David,

Ebright, Richard H,

Bird, Jeremy G,

Basu, Urmimala,

Ramachandran, Aparna,

Nickels, Bryce E

2018

Overview

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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Publisher

eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

Subject

Adenine

/ Adenosine

/ Biochemistry

/ Biochemistry and Chemical Biology

/ Chromosomes and Gene Expression

/ Cytoplasm - genetics

/ Cytoplasm - metabolism