Stress promotes RNA G-quadruplex folding in human cells.
Stress promotes RNA G-quadruplex folding in human cells.
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DOI：
10.1038/s41467-023-35811-x
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发表时间：
2023-01-13
影响因子：
16.6
通讯作者：
Ivanov, Pavel
中科院分区：
文献类型：
--
作者：
Kharel, Prakash;Fay, Marta;Manasova, Ekaterina V.;Anderson, Paul J.;Kurkin, Alexander V.;Guo, Junjie U.;Ivanov, Pavel
在允许的条件下，富含鸟嘌呤(G)的核酸可以折叠成G-四链(G4)结构。尽管许多RNA含有在体外折叠成RNA G4S(RG4s)的序列，但它们在体内的折叠和功能尚不清楚。在这份报告中，我们展示了在压力下，人类细胞中可能的rG4折叠成RG4结构的动态调节。通过使用高通量的二甲基硫酸酯(DMS)探针，我们识别了数百个内源性应激诱导的rG4，并使用RG4下拉方法对其进行了验证。我们的结果表明，应激诱导的rG4在mRNA3‘非翻译区富含，并增强了mRNA3’-非翻译区的稳定性。此外，应力诱导的Rg4折叠在应力消除后很容易逆转。综上所述，我们的研究揭示了Rg4折叠在人类细胞中的动态调节，并表明广泛存在的Rg4基序可能对mRNA的稳定性和细胞应激反应产生全球调控影响。RG4是转录组中发现的G-四链结构。许多RNA在体外可以折叠成rG4，但它们在体内的折叠和功能还不是很清楚。在这里，作者证明了在人类细胞中，rG4s折叠是在压力下动态调节的。
Guanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. In this report, we showed that the folding of putative rG4s in human cells into rG4 structures is dynamically regulated under stress. By using high-throughput dimethylsulfate (DMS) probing, we identified hundreds of endogenous stress-induced rG4s, and validated them by using an rG4 pull-down approach. Our results demonstrate that stress-induced rG4s are enriched in mRNA 3′-untranslated regions and enhance mRNA stability. Furthermore, stress-induced rG4 folding is readily reversible upon stress removal. In summary, our study revealed the dynamic regulation of rG4 folding in human cells and suggested that widespread rG4 motifs may have a global regulatory impact on mRNA stability and cellular stress response. rG4s are G-quadruplex structures found in transcriptome. Many RNAs can fold into rG4s in vitro, yet their folding and functions in vivo are not well understood. Here the authors showed that rG4s folding is dynamically regulated under stress in human cells.
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影响因子：
16.6
作者：
Lyons SM;Gudanis D;Coyne SM;Gdaniec Z;Ivanov P
通讯作者：
Ivanov P
影响因子：
21.8
作者：
Di Antonio M;Ponjavic A;Radzevičius A;Ranasinghe RT;Catalano M;Zhang X;Shen J;Needham LM;Lee SF;Klenerman D;Balasubramanian S
通讯作者：
Balasubramanian S
影响因子：
7.3
作者：
Kharel, Prakash;Balaratnam, Sumirtha;Basu, Soumitra
通讯作者：
Basu, Soumitra
影响因子：
8.8
作者：
Fay MM;Anderson PJ;Ivanov P
通讯作者：
Ivanov P
影响因子：
2.9
作者：
Morris, Mark J.;Basu, Soumitra
通讯作者：
Basu, Soumitra