Bacterial tRNA 2′-O-methylation is dynamically regulated under stress conditions and modulates innate immune response

Abstract

RNA modifications are a well-recognized way of gene expression regulation at the post-transcriptional level. Despite the importance of this level of regulation, current knowledge on modulation of tRNA modification status in response to stress conditions is far from being complete. While it is widely accepted that tRNA modifications are rather dynamic, such variations are mostly assessed in terms of total tRNA, with only a few instances where changes could be traced to single isoacceptor species. Using Escherichia coli as a model system, we explored stress-induced modulation of 2′-O-methylations in tRNAs by RiboMethSeq. This analysis and orthogonal analytical measurements by LC-MS show substantial, but not uniform, increase of the Gm18 level in selected tRNAs under mild bacteriostatic antibiotic stress, while other Nm modifications remain relatively constant. The absence of Gm18 modification in tRNAs leads to moderate alterations in E. coli mRNA transcriptome, but does not affect polysomal association of mRNAs. Interestingly, the subset of motility/chemiotaxis genes is significantly overexpressed in ΔTrmH mutant, this corroborates with increased swarming motility of the mutant strain. The stress-induced increase of tRNA Gm18 level, in turn, reduced immunostimulation properties of bacterial tRNAs, which is concordant with the previous observation that Gm18 is a suppressor of Toll-like receptor 7 (TLR7)-mediated interferon release. This documents an effect of stress induced modulation of tRNA modification that acts outside protein translation.

Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6

“…Alternatively, METTL2B possibly needs other unknown co-factors in catalyzing tRNA modification. On the other hand, tRNA modification has been shown to be highly dynamic in response to various stimuli or stresses ( 33 , 34 ). It is possible that the m 3 C32 modification level is precisely balanced based on the expression level or ratio of METTL2A and METTL2B, which is regulated in a tissue- or cell-specific manner.…”

The genetic and ecological landscape of plasmids in the human gut

“…S8, table S5). This enzyme is thought to reduce the immuno-stimulatory nature of bacterial tRNA, which is detected by Toll-like receptors (TLR7) of the mammalian innate immune system (67,68). While plasmids in some pathogens are known to facilitate bacterial evasion of mammalian immune system by regulating surface proteins (69), the overwhelming prevalence of tRNA modification enzymes in our data suggests the likely presence of a previously unappreciated role for plasmids to increase the fitness of their bacterial hosts against the survey of the human immune system.…”

RNA modifications stabilize the tertiary structure of tRNAfMet by locally increasing conformational dynamics

“…In general, it was shown that the degree of modification varies with growth and stress conditions, e.g. growth temperature or starvation ( 77 , 78 ). However, it was recently shown that the C m 32 modification of initiator tRNA fMet in E. coli is not affected by different growth conditions and temperatures ( 77 ).…”

“…growth temperature or starvation ( 77 , 78 ). However, it was recently shown that the C m 32 modification of initiator tRNA fMet in E. coli is not affected by different growth conditions and temperatures ( 77 ).…”