Depletion of S-adenosylmethionine impacts on ribosome biogenesis through hypomodification of a single rRNA methylation

Abstract

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 Δmtn 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 Δmtn strain with significant accumulation of 45S ribosomal precursor harboring 23S rRNA with hypomodified 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.