The helicase DHX36 resolves G-quadruplex structures and supports stress response
DNA and RNA G-quadruplex structures are thermodynamically very stable arrangements of four nucleic acid strands, in which the guanines interact via Hoogsteen base pairing. It has been shown that the formation or resolution of RNA G‑quadruplex structures has severe impacts on diverse cellular processes such as transcription or translation. Interestingly, the formation of G-quadruplex structures in untranslated regions of mRNAs can render these mRNAs translationally inactive. The Paeschke lab characterized the RNA targets of DHX36, a 3′−5′ DEAH-box helicase, and discovered that it performs an important function in resolving G-quadruplex structures in the 5´ and 3' untranslated regions of mRNAs. The deletion of DHX36 resulted in an increased formation of stress granules and the phosphorylation of protein kinase R (PKR), caused by the accumulation of G-quadruplex structures in the cytoplasm. PKR is an important factor for the innate immune system and the integrated stress response. PKR is activated upon phosphorylation, which leads to the shutdown of global protein synthesis. In summary, the Paeschke lab could demonstrate that G-quadruplex structures within mRNAs and the cellular stress response are connected and that this connection is established via DHX36 and PKR.
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