Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control,Cell Host & Microbe

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Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-08-01 , DOI: 10.1016/j.chom.2024.07.006
Philipp Schult ₁ , Beate Mareike Kümmerer ₂ , Markus Hafner ₃ , Katrin Paeschke ₁

Affiliation

Viral genomes are enriched with G-quadruplexes (G4s), non-canonical structures formed in DNA or RNA upon assembly of four guanine stretches into stacked quartets. Because of their critical roles, G4s are potential antiviral targets, yet their function remains largely unknown. Here, we characterize the formation and functions of a conserved G4 within the polymerase coding region of orthoflaviviruses of the Flaviviridae family. Using yellow fever virus, we determine that this G4 promotes viral replication and suppresses host stress responses via interactions with hnRNPH1, a host nuclear protein involved in RNA processing. G4 binding to hnRNPH1 causes its cytoplasmic retention with subsequent impacts on G4-containing tRNA fragments (tiRNAs) involved in stress-mediated reductions in translation. As a result, these host stress responses and associated antiviral effects are impaired. These data reveal that the interplay between hnRNPH1 and both host and viral G4 targets controls the integrated stress response and viral replication.

中文翻译：

hnRNPH1 的病毒劫持揭示了 G 四链体驱动的压力控制机制

病毒基因组富含 G 四链体（G4），这是 DNA 或 RNA 中在将四个鸟嘌呤片段组装成堆叠四链体后形成的非经典结构。由于其关键作用，G4 是潜在的抗病毒靶点，但它们的功能在很大程度上仍然未知。在这里，我们表征了黄病毒科正黄病毒聚合酶编码区内保守 G4 的形成和功能。使用黄热病病毒，我们确定这种 G4 通过与 hnRNPH1（一种参与 RNA 加工的宿主核蛋白）相互作用来促进病毒复制并抑制宿主应激反应。G4 与 hnRNPH1 的结合导致其细胞质滞留，随后影响参与应激介导的翻译减少的含 G4 的 tRNA 片段（tiRNA）。因此，这些宿主应激反应和相关的抗病毒作用受损。这些数据表明，hnRNPH1 与宿主和病毒 G4 靶标之间的相互作用控制着整合的应激反应和病毒复制。

更新日期：2024-08-01

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