Khoshnevis Sohail, Dreggors-Walker R Elizabeth, Marchand Virginie, Motorin Yuri, Ghalei Homa
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322.
Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2117334119. doi: 10.1073/pnas.2117334119. Epub 2022 Mar 16.
SignificanceThe presence of RNA chemical modifications has long been known, but their precise molecular consequences remain unknown. 2'--methylation is an abundant modification that exists in RNA in all domains of life. Ribosomal RNA (rRNA) represents a functionally important RNA that is heavily modified by 2'--methylations. Although abundant at functionally important regions of the rRNA, the contribution of 2'--methylations to ribosome activities is unknown. By establishing a method to disturb rRNA 2'--methylation patterns, we show that rRNA 2'--methylations affect the function and fidelity of the ribosome and change the balance between different ribosome conformational states. Our work links 2'--methylation to ribosome dynamics and defines a set of critical rRNA 2'--methylations required for ribosome biogenesis and others that are dispensable.
意义
RNA化学修饰的存在早已为人所知,但其精确的分子后果仍不清楚。2'-O-甲基化是一种广泛存在的修饰,存在于所有生命领域的RNA中。核糖体RNA(rRNA)是一种功能重要的RNA,被2'-O-甲基化大量修饰。尽管在rRNA的功能重要区域含量丰富,但2'-O-甲基化对核糖体活性的贡献尚不清楚。通过建立一种干扰rRNA 2'-O-甲基化模式的方法,我们表明rRNA 2'-O-甲基化影响核糖体的功能和保真度,并改变不同核糖体构象状态之间的平衡。我们的工作将2'-O-甲基化与核糖体动力学联系起来,并定义了一组核糖体生物发生所需的关键rRNA 2'-O-甲基化以及其他可有可无的甲基化。