2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family.

2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family.
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DOI:
10.1093/nar/gkr038
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发表时间:
2011-06
影响因子:
14.9
通讯作者:
Bujnicki JM
Bujnicki JM
中科院分区:
生物学2区
文献类型:
--
作者:
Werner M;Purta E;Kaminska KH;Cymerman IA;Campbell DA;Mittra B;Zamudio JR;Sturm NR;Jaworski J;Bujnicki JM

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人类信使 RNA 的 5' 帽由反向 7-甲基鸟苷组成,通过独特的 5'-5' 三磷酸键与第一个转录核苷酸连接,随后对第一个和通常是第二个转录核苷酸进行 2'-O-核糖甲基化,可能有助于改变转录物加工、翻译和稳定性的效率。我们报告了一种人类酶的验证,该酶可甲基化 FTSJD1 编码的第二个转录核苷酸的核糖,此后更名为 HMTR2 以反映功能。纯化的重组 hMTr2 蛋白将甲基从 S-腺苷甲硫氨酸转移到信使 RNA 和小核 RNA 的第二个核苷酸的 2'-O-核糖上。 hMTr2 不需要鸟苷帽的 N7 甲基化和第一个转录核苷酸的 2'-O-核糖甲基化,但 cap1 甲基化的存在会增加 hMTr2 的活性。与核 hMTr1 不同,hMTr2 蛋白分布在整个细胞核和细胞质中。特定转录本如何以及为何经历这些核糖甲基化修饰的细节仍有待阐明。 2'-O-核糖 RNA 帽甲基转移酶以不同的组合存在于大多数真核生物和许多病毒基因组中。有了封端酶,就可以确定其生物学目的。
The 5′ cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5′–5′ triphosphate bond followed by 2′-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. We report the validation of a human enzyme that methylates the ribose of the second transcribed nucleotide encoded by FTSJD1, henceforth renamed HMTR2 to reflect function. Purified recombinant hMTr2 protein transfers a methyl group from S-adenosylmethionine to the 2′-O-ribose of the second nucleotide of messenger RNA and small nuclear RNA. Neither N7 methylation of the guanosine cap nor 2′-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity. The hMTr2 protein is distributed throughout the nucleus and cytosol, in contrast to the nuclear hMTr1. The details of how and why specific transcripts undergo modification with these ribose methylations remains to be elucidated. The 2′-O-ribose RNA cap methyltransferases are present in varying combinations in most eukaryotic and many viral genomes. With the capping enzymes in hand their biological purpose can be ascertained.
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