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

Translation efficiencycan be affected by mRNA stability and secondary structures, including G-quadruplexstructures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36targets and function is lacking. We map globally DHX36binding to RNA in human cell linesand find it preferentiallyinteracting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36knockout (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 DHX36targets, harboring G4s, preferentiallylocalize in stress granules, and that DHX36KO results in increased SG formation and protein kinase R(PKR/EIF2AK2) phosphorylation, we speculate that DHX36is involved in resolution of rG4 induced cellular stress.