mRNA structure determines modification by pseudouridine synthase 1.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
16
11
2018
accepted:
22
07
2019
pubmed:
4
9
2019
medline:
19
11
2019
entrez:
4
9
2019
Statut:
ppublish
Résumé
Pseudouridine (Ψ) is a post-transcriptional RNA modification that alters RNA-RNA and RNA-protein interactions that affect gene expression. Messenger RNA pseudouridylation was recently discovered as a widespread and conserved phenomenon, but the mechanisms responsible for selective, regulated pseudouridylation of specific sequences within mRNAs were unknown. Here, we have revealed mRNA targets for five pseudouridine synthases and probed the determinants of mRNA target recognition by the predominant mRNA pseudouridylating enzyme, Pus1, by developing high-throughput kinetic analysis of pseudouridylation in vitro. Combining computational prediction and rational mutational analysis revealed an RNA structural motif that is both necessary and sufficient for mRNA pseudouridylation. Applying this structural context information predicted hundreds of additional mRNA targets that were pseudouridylated in vivo. These results demonstrate a structure-dependent mode of mRNA target recognition by a conserved pseudouridine synthase and implicate modulation of RNA structure as the probable mechanism to regulate mRNA pseudouridylation.
Identifiants
pubmed: 31477916
doi: 10.1038/s41589-019-0353-z
pii: 10.1038/s41589-019-0353-z
pmc: PMC6764900
mid: NIHMS1535497
doi:
Substances chimiques
RNA, Messenger
0
Hydro-Lyases
EC 4.2.1.-
pseudouridylate synthetase
EC 4.2.1.70
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
966-974Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM101316
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007287
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM087237
Pays : United States
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