The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure.
The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure.
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DOI：
10.1093/nar/gky637
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发表时间：
2018-09-06
影响因子：
14.9
通讯作者：
Decroly E
中科院分区：
文献类型：
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作者：
Martin B;Coutard B;Guez T;Paesen GC;Canard B;Debart F;Vasseur JJ;Grimes JM;Decroly E
单链病毒，如埃博拉病毒，编码一个L（大）蛋白，承担复制/转录和RNA盖帽的所有催化活性。L蛋白的c端保守区VI （CRVI）包含一个典型的2'O甲基转移酶（MTase）的K-D-K-E催化四联体。在单核病毒中，cap- mtase活性参与RNA帽结构的2'O甲基化和N7甲基化。这些活动在病毒生命周期中起着关键作用，因为N7甲基化确保了病毒mRNA的有效翻译，而2'O甲基化阻碍了宿主先天免疫对病毒RNA的检测。苏丹埃博拉病毒（SUDV） MTase+CTD结构域的功能表征揭示了针对内部腺苷残基的不依赖于帽的甲基转移酶活性。除此之外，如果RNA足够长，MTase+CTD也会甲基化，帽鸟苷的N7位置和n1鸟苷的2'O位置。总之，这些结果表明，线状病毒mtase进化成具有不同底物特异性的双重活性。尽管已经确定帽依赖性甲基化促进蛋白质翻译并有助于模仿宿主RNA，但对原始帽非依赖性甲基化的表征为阐明RNA内部甲基化在病毒复制中的作用开辟了新的研究机会。
Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all the catalytic activities for replication/transcription and RNA capping. The C-terminal conserved region VI (CRVI) of L protein contains a K-D-K-E catalytic tetrad typical for 2’O methyltransferases (MTase). In mononegaviruses, cap-MTase activities have been involved in the 2’O methylation and N7 methylation of the RNA cap structure. These activities play a critical role in the viral life cycle as N7 methylation ensures efficient viral mRNA translation and 2’O methylation hampers the detection of viral RNA by the host innate immunity. The functional characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap-independent methyltransferase activities targeting internal adenosine residues. Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine and the 2’O position of the n1 guanosine provided that the RNA is sufficiently long. Altogether, these results suggest that the filovirus MTases evolved towards a dual activity with distinct substrate specificities. Whereas it has been well established that cap-dependent methylations promote protein translation and help to mimic host RNA, the characterization of an original cap-independent methylation opens new research opportunities to elucidate the role of RNA internal methylations in the viral replication.
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影响因子：
3.7
作者：
Chung, Ka Yan;Dong, Hongping;Lim, Siew Pheng
通讯作者：
Lim, Siew Pheng
影响因子：
6.7
作者：
Decroly E;Debarnot C;Ferron F;Bouvet M;Coutard B;Imbert I;Gluais L;Papageorgiou N;Sharff A;Bricogne G;Ortiz-Lombardia M;Lescar J;Canard B
通讯作者：
Canard B
影响因子：
4.8
作者：
Hager, J;Staker, BL;Jakob, U
通讯作者：
Jakob, U
影响因子：
7.6
作者：
Barral, K.;Sallamand, C.;Decroly, E.
通讯作者：
Decroly, E.
病毒mRNA帽的2'-O甲基化通过IFIT家族成员逃避了宿主的限制。
影响因子：
64.8
作者：
通讯作者：
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