RT Journal Article SR Electronic T1 Translational regulation by bacterial small RNAs via an unusual Hfq-dependent mechanism JF bioRxiv FD Cold Spring Harbor Laboratory SP 169359 DO 10.1101/169359 A1 Muhammad S. Azam A1 Carin K. Vanderpool YR 2017 UL http://biorxiv.org/content/early/2017/07/28/169359.abstract AB In bacteria, the canonical mechanism of translational repression by small RNAs (sRNAs) involves sRNA-mRNA base pairing that occludes the ribosome binding site (RBS), directly preventing translation. In this mechanism, the sRNA is the direct regulator, while the RNA chaperone Hfq plays a supporting role by stabilizing the sRNA. There are a few examples where the sRNA does not directly interfere with ribosome binding, yet translation of the target mRNA is still inhibited. Mechanistically, this non-canonical regulation by sRNAs is very poorly understood. Our previous work demonstrated repression of the mannose transporter manX mRNA by the sRNA SgrS, but the regulatory mechanism was unknown. Here, we report that manX translation is controlled by a molecular role-reversal mechanism where Hfq, not the sRNA, is the direct repressor. Hfq binding adjacent to the manX RBS is required for sRNA-mediated translational repression. Translation of manX is also regulated by another sRNA, DicF, via the non-canonical Hfq-dependent mechanism. We posit that the sRNAs act to recruit Hfq to the appropriate binding site or stabilize the sRNA-mRNA-Hfq complex. This work adds to the growing number of examples of diverse mechanisms of translational regulation by sRNAs in bacteria.