A conserved structured non-coding RNA coordinates growth and virulence in Clostridioides difficile. [DMS-MaP]

ABSTRACT: Bacterial non-coding RNAs fulfill a variety of cellular functions, for example as catalysts of chemical reactions, as structural components in multiprotein complexes or as regulators of gene expression at the transcriptional and post-transcriptional level. Some RNAs, such as ribosomal RNAs, display exceptionally broad conservation across bacterial phyla and are involved in fundamental and unique cellular functions. Hence, the characterization of new RNA families with deep sequence and/or structure conservation has the potential to reveal new molecular and biological RNA functions. Here, we characterize the Clostridioides difficile ‘raiA motif’ RNA, which we rename ModT (modulator of transition phase), a member of an RNA family that is conserved in approx. 2,500 physiologically diverse bacterial species belonging to the phyla Bacillota and Actinomycetota. We show that ModT transcript abundance and stability in exponentially growing bacteria rivals that of ribosomal RNAs. Deletion of modT is associated with delayed transition into stationary phase, and changes in stationary phase pathways such as spore formation and toxin production. Mechanistically, we show that ModT-mediated changes in cellular cyclic di-GMP levels are linked to a pronounced sporulation defect in the modT mutant. ModT is produced in two isoforms that are largely identical in their secondary structure, but differ in their in vivo half-lives as well as their capacity to complement the sporulation phenotype of the modT mutant. Importantly, we show that expression profiles and isoform patterns of ModT are conserved in C. perfringens and P. sordellii, and that these orthologs can functionally replace ModT in C. difficile. In summary, we provide functional evidence that ModT fulfills a conserved biochemical function in bacteria that is likely enabled by its complex tertiary structure.

ORGANISM(S): Clostridioides difficile

PROVIDER: GSE273118 | GEO | 2024/10/31

REPOSITORIES: GEO