DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 06 2019
03 06 2019
Historique:
received:
04
12
2018
accepted:
07
05
2019
entrez:
5
6
2019
pubmed:
5
6
2019
medline:
25
6
2019
Statut:
epublish
Résumé
Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.
Identifiants
pubmed: 31160600
doi: 10.1038/s41467-019-10432-5
pii: 10.1038/s41467-019-10432-5
pmc: PMC6547686
doi:
Substances chimiques
RNA, Messenger
0
Untranslated Regions
0
EIF2AK2 protein, human
EC 2.7.11.1
eIF-2 Kinase
EC 2.7.11.1
DHX36 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2421Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC2151 - 390873048
Pays : International
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Euratom (H2020 Euratom Research and Training Programme 2014-2018)
ID : 638988-G4DSB
Pays : International
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