Molecular mechanism of RNase R substrate sensitivity for RNA ribose methylation.
Molecular mechanism of RNase R substrate sensitivity for RNA ribose methylation.
复制标题
RNase R底物对RNA核糖甲基化敏感性的分子机制
DOI：
10.1093/nar/gkab202
复制
发表时间：
2021-05-07
影响因子：
14.9
通讯作者：
Ji X
中科院分区：
文献类型：
--
作者：
Abula A;Li X;Quan X;Yang T;Liu Y;Guo H;Li T;Ji X
RNA 2'-O-甲基化广泛分布，并在各种细胞过程中起重要作用。然而，对RNA 2'-O-甲基化的敏感我们报告了Apo形式的MGR的高分辨率晶体结构，并与各种RNA底物进行了复杂的结构数据。通过结构和诱变研究揭示了RNA底物的识别和降解的独家机制。 Proline 277负责RNASE II/RNB家族中MGR对RNA 2'-O-甲基化的显着敏感性。作为强大的RNA分析工具，将为生物和临床样品中的RNA 2'-O-甲基化研究开放新的场所。
RNA 2′-O-methylation is widely distributed and plays important roles in various cellular processes. Mycoplasma genitalium RNase R (MgR), a prokaryotic member of the RNase II/RNB family, is a 3′-5′ exoribonuclease and is particularly sensitive to RNA 2′-O-methylation. However, how RNase R interacts with various RNA species and exhibits remarkable sensitivity to substrate 2′-O-methyl modifications remains elusive. Here we report high-resolution crystal structures of MgR in apo form and in complex with various RNA substrates. The structural data together with extensive biochemical analysis quantitively illustrate MgR’s ribonuclease activity and significant sensitivity to RNA 2′-O-methylation. Comparison to its related homologs reveals an exquisite mechanism for the recognition and degradation of RNA substrates. Through structural and mutagenesis studies, we identified proline 277 to be responsible for the significant sensitivity of MgR to RNA 2′-O-methylation within the RNase II/RNB family. We also generated several MgR variants with modulated activities. Our work provides a mechanistic understanding of MgR activity that can be harnessed as a powerful RNA analytical tool that will open up a new venue for RNA 2′-O-methylations research in biological and clinical samples.
登录
查看更多内容
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16.6
作者：
Birkedal, Ulf;Christensen-Dalsgaard, Mikkel;Nielsen, Henrik
通讯作者：
Nielsen, Henrik
影响因子：
3.2
作者：
Awano, Naoki;Rajagopal, Vaishnavi;Phadtare, Sangita
通讯作者：
Phadtare, Sangita
影响因子：
4.1
作者：
Barria, Catia;Domingues, Susana;Arraiano, Cecilia Maria
通讯作者：
Arraiano, Cecilia Maria
影响因子：
56.9
作者：
FRASER, CM;GOCAYNE, JD;VENTER, JC
通讯作者：
VENTER, JC