小柯机器人

美国国立卫生研究院的Schraga Schwartz研究团队取得最新进展。他们的论文发现定量交叉进化图谱揭示了动态RNA乙酰化。2020年6月17日，《自然》发表了该成果。

他们报告了N4-乙酰胞苷（ac4C）-seq，这种化学基因组学方法，可用于在单核苷酸分辨率下对ac4C进行转录组范围的定量定位。在人和酵母mRNA中，未检测到ac4C位点，但可以通过在保守的序列基序上异位过表达真核乙酰转移酶复合物的来诱导它。相比之下，交叉进化分析揭示了超嗜热古细菌中rRNA、tRNA、非编码RNA和mRNA中数百个残基的ac4C水平达到空前水平。

Ac4C响应温度的升高而明显被诱导，并且乙酰转移酶缺陷的古细菌菌株表现出温度依赖性的生长缺陷。野生型和乙酰转移酶缺陷古细菌核糖体的冷冻电镜可视化，提供了对ac4C的温度依赖性分布及其潜在热适应作用的结构见解。他们的研究定量定义了ac4C领域，为阐明这种修饰在生物学和疾病中的作用提供了技术和概念基础。

据介绍，ac4C是存在于tRNA和rRNA上的古老且高度保守的RNA修饰，最近已在真核mRNA中进行了研究。然而，胞苷乙酰化的分布，动力学和功能尚未完全阐明。

附：英文原文

Title: Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping

Author: Aldema Sas-Chen, Justin M. Thomas, Donna Matzov, Masato Taoka, Kellie D. Nance, Ronit Nir, Keri M. Bryson, Ran Shachar, Geraldy L. S. Liman, Brett W. Burkhart, Supuni Thalalla Gamage, Yuko Nobe, Chloe A. Briney, Michaella J. Levy, Ryan T. Fuchs, G. Brett Robb, Jesse Hartmann, Sunny Sharma, Qishan Lin, Laurence Florens, Michael P. Washburn, Toshiaki Isobe, Thomas J. Santangelo, Moran Shalev-Benami, Jordan L. Meier, Schraga Schwartz

Issue&Volume: 2020-06-17

Abstract: N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA1,2,3. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac4C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac4C at single-nucleotide resolution. In human and yeast mRNAs, ac4C sites are not detected but can be induced—at a conserved sequence motif—via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac4C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac4C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac4C and its potential thermoadaptive role. Our studies quantitatively define the ac4C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease4,5,6.

DOI: 10.1038/s41586-020-2418-2

Source: https://www.nature.com/articles/s41586-020-2418-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html