18S rRNA 甲基化多重性对翻译的调控。

Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.

Cell Rep. 2021 Mar 9;34(10):108825. doi: 10.1016/j.celrep.2021.108825.

N-methyladenosine (mA) is a conserved ribonucleoside modification that regulates many facets of RNA metabolism. Using quantitative mass spectrometry, we find that the universally conserved tandem adenosines at the 3' end of 18S rRNA, thought to be constitutively di-methylated (mA), are also mono-methylated (mA). Although present at substoichiometric amounts, mA at these positions increases significantly in response to sulfur starvation in yeast cells and mammalian cell lines. Combining yeast genetics and ribosome profiling, we provide evidence to suggest that mA-bearing ribosomes carry out translation distinctly from mA-bearing ribosomes, featuring a striking specificity for sulfur metabolism genes. Our work thus reveals methylation multiplicity as a mechanism to regulate translation.

N6-甲基腺嘌呤（m6A）是一种保守的核糖核苷修饰，调节 RNA 代谢的多个方面。使用定量质谱法，我们发现 18S rRNA 3' 末端普遍保守的腺苷串联，被认为是组成性二甲基化（m6A），也是单甲基化（m6A）。尽管 m6A 以亚化学计量存在，但在酵母细胞和哺乳动物细胞系中硫饥饿时，这些位置的 m6A 显著增加。通过结合酵母遗传学和核糖体图谱分析，我们提供的证据表明，携带 m6A 的核糖体与携带 m6A 的核糖体进行翻译的方式明显不同，对硫代谢基因具有惊人的特异性。因此，我们的工作揭示了甲基化多样性作为调节翻译的一种机制。