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Nat Commun. 2019 Jun 3;10(1):2421. doi: 10.1038/s41467-019-10432-5.

DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions.

Author information

1
Department of Biochemistry, Biocenter, University of Würzburg, 97074, Würzburg, Germany.
2
European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands.
3
Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, 53127, Bonn, Germany.
4
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 20892, USA.
5
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 20892, USA. markus.hafner@nih.gov.
6
Department of Biochemistry, Biocenter, University of Würzburg, 97074, Würzburg, Germany. katrin.paeschke@ukbonn.de.
7
European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands. katrin.paeschke@ukbonn.de.
8
Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, 53127, Bonn, Germany. katrin.paeschke@ukbonn.de.

Abstract

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.

PMID:
31160600
PMCID:
PMC6547686
DOI:
10.1038/s41467-019-10432-5
[Indexed for MEDLINE]
Free PMC Article

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