Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms and can arise from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated. We used RiboMeth-seq to demonstrate that differential 2′-O-methylation of ribosomal RNA (rRNA) represents a considerable source of ribosome heterogeneity in human cells, and that modification levels at distinct sites can change dynamically in response to upstream signaling pathways, such as MYC oncogene expression. Ablation of one prominent methylation resulted in altered translation of select mRNAs and corresponding changes in cellular phenotypes. Thus, differential rRNA 2′-O-methylation can give rise to ribosomes with specialized function. This suggests a broader mechanism where the specific regulation of rRNA modification patterns fine tunes translation.

核糖体是复杂的核酶，通过将信使 RNA (mRNA) 翻译成蛋白质来解释遗传信息。核糖体组成的自然变异已在几种生物体中得到证实，并且可能来自几种不同的来源。一个关键问题是对核糖体异质性的特定控制是否代表了一种可以调节翻译的机制。我们使用 RiboMeth-seq 来证明核糖体 RNA (rRNA) 的差异 2'-O-甲基化代表了人类细胞中核糖体异质性的重要来源，并且不同位点的修饰水平可以响应上游信号通路而动态变化，例如作为MYC癌基因表达。消除一种显着的甲基化会导致选定 mRNA 的翻译发生改变，并导致细胞表型发生相应的变化。因此，差异 rRNA 2'-O-甲基化可以产生具有特殊功能的核糖体。这表明了一种更广泛的机制，其中 rRNA 修饰模式的特定调节微调翻译。