Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA.

Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA.
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整个转录组的映射揭示了包括mRNA在内的二氢岛景观。

DOI:
10.1371/journal.pbio.3001622
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发表时间:
2022-05
期刊:
影响因子:
9.8
通讯作者:
Gilbert, Wendy, V
Gilbert, Wendy, V
中科院分区:
生物学1区
文献类型:
--
作者:
Draycott, Austin S.;Schaening-Burgos, Cassandra;Rojas-Duran, Maria F.;Wilson, Loren;Scharfen, Leonard;Neugebauer, Karla M.;Nachtergaele, Sigrid;Gilbert, Wendy, V

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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. This study presents dihydrouridine sequencing (D-seq) for transcriptome-wide mapping of this RNA modification with single-nucleotide resolution, revealing dihydrouridine at new locations across the yeast transcriptome that suggest a broad role in folding functional RNA structures.
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