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首页> 美国卫生研究院文献>Nature Communications >DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
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DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions

机译：DHX36防止未翻译区域中具有G4结构的翻译无效mRNA的积累

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摘要

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.
机译：mRNA的稳定性和二级结构（包括G-四链体结构（G4s））会影响翻译效率。高度保守的DEAH-box解旋酶DHX36 / RHAU可以在体外分辨DNA和RNA上的G4，但是缺乏对DHX36靶标和功能的系统性分析。我们将DHX36与人类细胞系中的RNA结合的全球图谱，发现它优先与超过4500种mRNA的富含G和G4的序列相互作用。虽然DHX36敲除（KO）会导致靶标mRNA的丰度显着增加，但这些靶标的核糖体占有率和蛋白质输出降低，表明它们在翻译上不称职。考虑到DHX36靶标具有G4，优先定位在应激颗粒中，并且DHX36 KO导致SG形成增加和蛋白激酶R（PKR / EIF2AK2）磷酸化，我们推测DHX36参与了rG4诱导的细胞应激的缓解。

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