Regulation outside the box: New mechanisms for small RNAs

Regulation at the post‐transcriptional level is an important mode of gene expression control in bacteria. Small RNA regulators (sRNAs) that act via intramolecular base‐pairing with target mRNAs are key players in this process and most often sequester the target's ribosome binding site (RBS) to down‐regulate translation initiation. Over the past few years, several exceptions from this mechanism have been reported, revealing that sRNAs are able to influence translation initiation from a distance. In this issue of Molecular Microbiology, Azam and Vanderpool show that repression of the manY mRNA by the sRNA SgrS relies on an unconventional mechanism involving a translational enhancer element and ribosomal protein S1. Binding of S1 to an AU‐rich sequence within the 5ʹ untranslated region of the manY transcript promotes translation of the mRNA, and base‐pairing of SgrS to the same site can interfere with this process. Therefore, instead of blocking translation initiation by occluding the manY RBS, SgrS reduces ManY synthesis by inhibiting S1‐dependent translation activation. These findings increase the base‐pairing window for sRNA‐mediated gene expression control in bacteria and highlight the role of ribosomal protein S1 for translation initiation.