Depletion of S-adenosylmethionine impacts on ribosome biogenesis through hypomodification of a single rRNA methylation
Depletion of S-adenosylmethionine impacts on ribosome biogenesis through hypomodification of a single rRNA methylation
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DOI：
10.1093/nar/gkz111
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发表时间：
2019-05-07
影响因子：
14.9
通讯作者：
Suzuki, Tsutomu
中科院分区：
文献类型：
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作者：
Ishiguro, Kensuke;Arai, Taiga;Suzuki, Tsutomu
S-腺苷甲硫氨酸（SAM）是所有生物体的必需代谢产物和甲基供体。细胞内SAM浓度受到严格调节，并且耗尽导致底物的低甲基化、生长缺陷和病理后果。在新兴的表转录组学领域，SAM依赖的RNA甲基化在基因表达中起着关键作用。在此，我们分析了大肠杆菌Delta mtn菌株中核糖体RNA（rRNA）和转运RNA（tRNA）的甲基化状态，在该菌株中细胞SAM被下调，并发现几个甲基化位点的低修饰，包括23 S rRNA的2552位（Um 2552）的2 '-O-甲基化。我们观察到Delta mtn菌株的严重生长缺陷，具有携带23 S rRNA的45 S核糖体前体与低修饰Um 2552的显著积累。引人注目的是，生长缺陷部分恢复rlmE编码SAM依赖性甲基转移酶负责Um 2552的过表达。虽然SAM不仅参与rRNA甲基化，而且参与各种细胞过程，但对核糖体生物合成的影响实质上有助于观察到的细胞增殖缺陷。
S-adenosylmethionine (SAM) is an essential metabolite and a methyl group donor in all living organisms. The intracellular SAM concentration is tightly regulated, and depletion causes hypomethylation of substrates, growth defects and pathological consequences. In the emerging field of epitranscriptomics, SAM-dependent RNA methylations play a critical role in gene expression. Herein, we analyzed the methylation status of ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) in Escherichia coli Delta mtn strain in which cellular SAM was down-regulated, and found hypomodification of several methylation sites, including 2'-O-methylation at position 2552 (Um2552) of 23S rRNA. We observed severe growth defect of the Delta mtn strain with significant accumulation of 45S ribosomal precursor harboring 23S rRNA with hypo-modified Um2552. Strikingly, the growth defect was partially restored by overexpression of rlmE encoding the SAM-dependent methyltransferase responsible for Um2552. Although SAM is involved not only in rRNA methylation but also in various cellular processes, effects on ribosome biogenesis contribute substantially to the observed defects on cell proliferation.