Highly efficient 5' capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 12, 2018
- Source ID
- 10.7554/elife.42179
Entities
People
- Aparna Ramachandran
- Atif Towheed
- Bryce Nickels
- David Kuster
- Dmitry Temiakov
- Douglas C Wallace
- Ewa Grudzien-nogalska
- Jeremy G Bird
- Megerditch Kiledjian
- Richard H. Ebright
- Smita S Patel
- Urmimala Basu
Organizations
- American Heart Association
- Children's Hospital of Philadelphia
- Heidelberg University
- National Institutes of Health
- Perelman School of Medicine at the University of Pennsylvania
- Robert Wood Johnson Medical School
- Rutgers University
- Thomas Jefferson University
- United States Department of Defense