Proteomics

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Epitranscriptomic regulation of the oxidative stress response by the radical S-adenosylmethionine methyltransferase RlmN

ABSTRACT: Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogen Enterococcus faecalis. Following exposure to menadione or sublethal doses of ROS-inducing erythromycin and chloramphenicol, analysis of 25 modified ribonucleosides of the epitranscriptome revealed large decreases in N2-methyladenosine (m2A) in both 23S ribosomal RNA (rRNA) and transfer RNA (tRNA) caused by ROS-mediated inactivation of the Fe-S cluster-containing methyltransferase, RlmN. Loss of RlmN altered protein expression in a way that mimicked menadione exposure, such as increased superoxide dismutase and decreased virulence proteins. These studies suggest that RlmN acts as a redox-sensitive molecular switch that links environmental and antibiotic-induced ROS exposure to epitranscriptome dynamics in ribosomal and transfer RNA to effect translation of stress response proteins.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Enterococcus Faecalis (streptococcus Faecalis)

SUBMITTER: AMEYA SINHA  

LAB HEAD: Peter Dedon

PROVIDER: PXD038178 | Pride | 2023-05-09

REPOSITORIES: Pride

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20190510_WeiLin_SetA_F1.raw Raw
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Publications

An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis.

Lee Wei Lin WL   Sinha Ameya A   Lam Ling Ning LN   Loo Hooi Linn HL   Liang Jiaqi J   Ho Peiying P   Cui Liang L   Chan Cheryl Siew Choo CSC   Begley Thomas T   Kline Kimberly Ann KA   Dedon Peter P  

Nature communications 20230711 1

Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogen Enterococcus faecalis. We analyze the tRNA epitranscriptome of E. faecalis in response to reactive oxygen species (ROS) or sublethal doses of ROS-inducing antib  ...[more]

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