Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells.
Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells.
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胚胎干细胞内源性逆转录酶和RNase H介导的抗病毒机制
DOI：
10.1038/s41422-021-00524-7
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发表时间：
2021-09
期刊：
影响因子：
44.1
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Wu J;Wu C;Xing F;Cao L;Zeng W;Guo L;Li P;Zhong Y;Jiang H;Luo M;Shi G;Bu L;Ji Y;Hou P;Peng H;Huang J;Li C;Guo D
基于核酸的系统在抗病毒防御中发挥重要作用，包括采用RNA引导的DNA切割来防止DNA噬菌体感染的CRISPR/Cas和采用RNA引导的RNA切割来防御RNA病毒感染的RNA干扰（RNAi）。在这里，我们报告了一种新型的基于核酸的抗病毒系统，存在于小鼠胚胎干细胞（mESC），抑制RNA病毒感染的DNA介导的RNA切割。我们发现，脑心肌炎病毒的病毒RNA可以逆转录成互补DNA（vcDNA）的逆转录酶（RTase）编码的内源性逆转录病毒样元件在mESCs。vcDNA为负链单链，与病毒RNA形成DNA/RNA杂交体。异源双链体中的病毒RNA随后被细胞RNA酶H1破坏，导致对病毒生长的强力抑制。此外，抑制RT酶活性或耗尽内源性RNA酶H1导致促进病毒增殖。总之，我们的研究结果提供了有趣的见解mESCs的抗病毒机制和内源性逆转录病毒和细胞RNase H的抗病毒功能。mESC中这种天然的基于核酸的抗病毒机制被称为ERASE（内源性RTase/RNase H介导的抗病毒系统），它是对先前已知的基于核酸的抗病毒机制的补充，包括细菌中的CRISPR/Cas和植物和无脊椎动物中的RNAi。
Nucleic acid-based systems play important roles in antiviral defense, including CRISPR/Cas that adopts RNA-guided DNA cleavage to prevent DNA phage infection and RNA interference (RNAi) that employs RNA-guided RNA cleavage to defend against RNA virus infection. Here, we report a novel type of nucleic acid-based antiviral system that exists in mouse embryonic stem cells (mESCs), which suppresses RNA virus infection by DNA-mediated RNA cleavage. We found that the viral RNA of encephalomyocarditis virus can be reverse transcribed into complementary DNA (vcDNA) by the reverse transcriptase (RTase) encoded by endogenous retrovirus-like elements in mESCs. The vcDNA is negative-sense single-stranded and forms DNA/RNA hybrid with viral RNA. The viral RNA in the heteroduplex is subsequently destroyed by cellular RNase H1, leading to robust suppression of viral growth. Furthermore, either inhibition of the RTase activity or depletion of endogenous RNase H1 results in the promotion of virus proliferation. Altogether, our results provide intriguing insights into the antiviral mechanism of mESCs and the antiviral function of endogenized retroviruses and cellular RNase H. Such a natural nucleic acid-based antiviral mechanism in mESCs is referred to as ERASE (endogenous RTase/RNase H-mediated antiviral system), which is an addition to the previously known nucleic acid-based antiviral mechanisms including CRISPR/Cas in bacteria and RNAi in plants and invertebrates.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
DOI：
10.1126/science.aba0372
发表时间：
2020-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gao L;Altae-Tran H;Böhning F;Makarova KS;Segel M;Schmid-Burgk JL;Koob J;Wolf YI;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
30.5
作者：
Goic, Bertsy;Vodovar, Nicolas;Saleh, Maria-Carla
通讯作者：
Saleh, Maria-Carla
DOI：
10.1007/978-1-4939-1215-5_13
发表时间：
2014-01-01
期刊：
MOUSE GENETICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Jain, Kanika;Verma, Paul J.;Liu, Jun
通讯作者：
Liu, Jun
R环的形成是未甲基化的人类CpG岛启动子的独特特征。
影响因子：
16
作者：
Ginno PA;Lott PL;Christensen HC;Korf I;Chédin F
通讯作者：
Chédin F