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 5' 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.