Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA
Name
journal.pbio.3001622.pdf
Description
Published version
Size
3.2 MB
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Adobe PDF
Checksum (MD5)
f06ad8b7899aa085c4611a7dbfc71661
Author(s)
Draycott, Austin S
Schaening-Burgos, Cassandra
Rojas-Duran, Maria F
Wilson, Loren
Schärfen, Leonard
Neugebauer, Karla M
Nachtergaele, Sigrid
Gilbert, Wendy V
Date Issued
May 24, 2022
Journal
PLOS Biology
Publisher
Public Library of Science (PLoS)
Citation
Draycott AS, Schaening-Burgos C, Rojas-Duran MF, Wilson L, Schärfen L, Neugebauer KM, et al. (2022) Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA. PLoS Biol 20(5): e3001622.
Version
Final published version
Abstract
Dihydrouridine is a modified nucleotide universally present in tRNAs, but the complete dihydrouridine landscape is unknown in any organism. We introduce dihydrouridine sequencing (D-seq) for transcriptome-wide mapping of D with single-nucleotide resolution and use it to uncover novel classes of dihydrouridine-containing RNA in yeast which include mRNA and small nucleolar RNA (snoRNA). The novel D sites are concentrated in conserved stem-loop regions consistent with a role for D in folding many functional RNA structures. We demonstrate dihydrouridine synthase (DUS)-dependent changes in splicing of a D-containing pre-mRNA in cells and show that D-modified mRNAs can be efficiently translated by eukaryotic ribosomes in vitro. This work establishes D as a new functional component of the mRNA epitranscriptome and paves the way for identifying the RNA targets of multiple DUS enzymes that are dysregulated in human disease.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1371/journal.pbio.3001622
