TY - JOUR
T1 - DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
AU - Sauer, Markus
AU - Juranek, Stefan A.
AU - Marks, James
AU - De Magis, Alessio
AU - Kazemier, Hinke G.
AU - Hilbig, Daniel
AU - Benhalevy, Daniel
AU - Wang, Xiantao
AU - Hafner, Markus
AU - Paeschke, Katrin
N1 - Publisher Copyright:
© 2019, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066637593&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-10432-5
DO - 10.1038/s41467-019-10432-5
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C2 - 31160600
AN - SCOPUS:85066637593
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2421
ER -
