Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA

• DOI: 10.1371/journal.pbio.3001622
• Publication Date: 2022-05-24T22:04:22Z
• Authors: Austin S. Draycott; Cassandra Schaeni...; Maria F. Rojas-Duran; Loren Wilson; Leonard Schärfen; Karla M. Neugebauer; Sigrid Nachtergaele; Wendy V. Gilbert
• Keywords: Small nucleolar RNA; Small nuclear RNA

Dihydrouridine is a modified nucleotide universally present in tRNAs, but the complete dihydrouridine landscape unknown any organism. We introduce sequencing (D-seq) for transcriptome-wide mapping of D with single-nucleotide resolution and use it to uncover novel classes dihydrouridine-containing RNA yeast which include mRNA small nucleolar (snoRNA). The sites are concentrated conserved stem-loop regions consistent role folding many functional structures. demonstrate synthase (DUS)-dependent changes splicing D-containing pre-mRNA cells show that D-modified mRNAs can be efficiently translated by eukaryotic ribosomes vitro. This work establishes as new component epitranscriptome paves way identifying targets multiple DUS enzymes dysregulated human disease.