Small RNAs promote mRNA stability to activate the synthesis of virulence factors

Abstract

SummaryAlthough most bacterial small RNAs act to repress target mRNAs, some also activate messengers. The predominant mode of activation has been seen in 'anti-antisense' regulation whereby a small RNA prevents the formation of an inhibitory 5Ј mRNA structure that otherwise impairs translational initiation and protein synthesis. The translational activation might also stabilize the target yet this was considered a secondary effect in the examples known thus far. Two recent papers in Molecular Microbiology investigate post-transcriptional activation of collagenase mRNA by Clostridium VR-RNA, and streptokinase mRNA by Streptococcus FasX RNA, to suggest that small RNAs exert positive regulation of virulence genes primarily at the level of mRNA stabilization.

RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA

“…sRNAs commonly act on their target mRNA near the translation initiation site by base pairing to block-and in some cases promote-translation. Some sRNAs cause alterations in the secondary structure of the target mRNA, thereby enhancing or reducing mRNA degradation (3,4).…”

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

“…This is consistent with the important observations made recently by Ouellette et al (99), who showed that transcription and translation are uncoupled in Chlamydia and that transcripts made in the absence of translation can be quite stable. This scenario might be enhanced further if the recent contention that small RNAs promote mRNA stability to activate the synthesis of virulence factors (106) proves to apply to chlamydiae.…”

Small RNAs in streptococci

“…18 RamirezPena et al recently showed that the difference in activity could be partially explained by direct regulation of ska expression by the sRNA at the posttranscriptional level. 18 The report by Ramirez-Pena et al provided several lines of evidence for a novel mechanism wherein FasX exerts a positive regulation on Ska at the level of mRNA stabilization 18,50 (Fig. 3A).…”

“…18 It is possible that binding of FasX to the 5' end of ska mRNA would also activate translation initiation by promoting structural changes within the 5'UTR that would favor the accessibility of the ribosome to bind the mRNA. 18,50 In addition, given the influence of FasX on the interaction between S. pyogenes and its host, it would not be surprising to discover that FasX directly targets other mRNAs by using distinct modes of interaction, as exemplified by RNAIII of the Agr system in S. aureus. Future studies will reveal whether enhanced expression of targets via sRNA-mediated stabilization of base-paired structure formation at the 5' end of their mRNAs apply to streptococcal sRNAs other than FasX.…”