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

Nucleic Acids Research
Kensuke IshiguroTsutomu Suzuki

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.

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Citations

Dec 6, 2019·Nature Communications·Mayuko TakakuraTsutomu Suzuki
Apr 18, 2020·Wiley Interdisciplinary Reviews. RNA·Phillip J McCownJessica A Brown
Jun 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wei WangNing Gao
Nov 18, 2020·The Journal of Biological Chemistry·Sunil Shetty, Umesh Varshney
Jul 2, 2020·Current Opinion in Structural Biology·Simone Höfler, Teresa Carlomagno
Jan 19, 2021·The Journal of Biological Chemistry·Sunil Shetty, Umesh Varshney

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Methods Mentioned

BETA
GTPase
electrophoresis
PCR
ribosylation

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