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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-227486
  • 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 occupancyTranslation 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.show moreshow less

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Metadaten
Author: Markus Sauer, Stefan A. Juranek, James Marks, Alessio De Magis, Hinke G Kazemier, Daniel Hilbig, Daniel Benhalevy, Xiantao Wang, Markus Hafner, Katrin Paeschke
URN:urn:nbn:de:bvb:20-opus-227486
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Nature Communications
Year of Completion:2019
Volume:10
Issue:2421
Pagenumber:1-15
Source:Nat Commun 10, 2421 (2019)
DOI:https://doi.org/10.1038/s41467-019-10432-5
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:RNA metabolism; Translation
Release Date:2021/12/21
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International