小柯机器人

德国尤利乌斯-马克西米利安-维尔茨堡大学Claudia Höbartner研究团队，宣布发现由甲基转移酶核酶催化的位点特异性RNA甲基化。相关论文在线发表在2020年10月28日的《自然》杂志上。

在本研究中，研究人员发现了一种甲基转移酶核酶，该酶使用O⁶-甲基鸟嘌呤作为小分子辅因子催化底物RNA的1-甲基腺苷的甲基化。核酶可修饰广泛的RNA序列，例如各种RNA中位点特异性的腺苷甲基化。该发现丰富了对RNA催化能力的基本见解，为在RNA中添加1-甲基腺苷修饰提供了一种合成工具，并可能为其他甲基转移酶和脱甲基酶核酶的体外合成铺平道路。

据了解，几乎所有编码和非编码RNA都会发生转录后修饰，包括RNA甲基化。甲基化核苷酸是转移（t）RNA和核糖体（r）RNA进化上最保守的特征之一。许多已知甲基转移酶都使用辅助因子S-腺苷甲硫氨酸（SAM）作为甲基供体。SAM和其他核苷酸衍生辅助因子被认为是RNA进化的遗留物，其中核酶可能参与催化除自我复制外的其他基本代谢反应。核酶的化学多样性似乎已在自然界中丢失，但可以通过体外选择在实验室中重建。

附：英文原文

Title: Site-specific RNA methylation by a methyltransferase ribozyme

Author: Carolin P. M. Scheitl, Mohammad Ghaem Maghami, Ann-Kathrin Lenz, Claudia Hbartner

Issue&Volume: 2020-10-28

Abstract: Nearly all classes of coding and non-coding RNA undergo post-transcriptional modification, including RNA methylation. Methylated nucleotides are among the evolutionarily most-conserved features of transfer (t)RNA and ribosomal (r)RNA1,2. Many contemporary methyltransferases use the universal cofactor S-adenosylmethionine (SAM) as a methyl-group donor. SAM and other nucleotide-derived cofactors are considered to be evolutionary leftovers from an RNA world, in which ribozymes may have catalysed essential metabolic reactions beyond self-replication3. Chemically diverse ribozymes seem to have been lost in nature, but may be reconstructed in the laboratory by in vitro selection. Here we report a methyltransferase ribozyme that catalyses the site-specific installation of 1-methyladenosine in a substrate RNA, using O6-methylguanine as a small-molecule cofactor. The ribozyme shows a broad RNA-sequence scope, as exemplified by site-specific adenosine methylation in various RNAs. This finding provides fundamental insights into the catalytic abilities of RNA, serves a synthetic tool to install 1-methyladenosine in RNA and may pave the way to in vitro evolution of other methyltransferase and demethylase ribozymes. A methyltransferase ribozyme, along with the small-molecule cofactor O6-methylguanine, is shown to catalyse the site-specific installation of 1-methyladenosine in various RNAs, providing insights into the catalytic abilities of RNA.

DOI: 10.1038/s41586-020-2854-z

Source: https://www.nature.com/articles/s41586-020-2854-z

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