TY - JOUR
T1 - Translational regulation by bacterial small RNAs via an unusual Hfq-dependent mechanism
AU - Azam, Muhammad S.
AU - Vanderpool, Carin K.
N1 - Funding Information:
We thank members of the Vanderpool laboratory and the laboratory of James Slauch for productive discussions and Peter Orlean for sharing equipment important for carrying out experiments. Eric Massé and his lab members for advice and critical reading of the manuscript. We are grateful to Raya Romm, Hannah Margalit, Jai Tree and David Tollervey for sharing their analyses and interpretation of Hfq and RNase E cross-linking datasets. National Institutes of Health [R01 GM092830 and R01 GM112659]. Funding for open access charge: National Institutes of Health.
Funding Information:
National Institutes of Health [R01 GM092830 and R01 GM112659]. Funding for open access charge: National Institutes of Health. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2018/3/16
Y1 - 2018/3/16
N2 - 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 poorly understood. Our previous work demonstrated repression of the mannose transportermanXmRNA by the sRNA SgrS, but the regulatory mechanism was unknown. Here, we report that manX translation is controlled by a molecular rolereversal 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 same non-canonical Hfqdependent mechanism. Our results suggest that the sRNAs recruit Hfq to its binding site or stabilize the mRNA-Hfq complex. This work adds to the growing number of examples of diverse mechanisms of translational regulation by sRNAs in bacteria.
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 poorly understood. Our previous work demonstrated repression of the mannose transportermanXmRNA by the sRNA SgrS, but the regulatory mechanism was unknown. Here, we report that manX translation is controlled by a molecular rolereversal 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 same non-canonical Hfqdependent mechanism. Our results suggest that the sRNAs recruit Hfq to its binding site or stabilize the mRNA-Hfq complex. This work adds to the growing number of examples of diverse mechanisms of translational regulation by sRNAs in bacteria.
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U2 - 10.1093/nar/gkx1286
DO - 10.1093/nar/gkx1286
M3 - Article
C2 - 29294046
AN - SCOPUS:85048677190
SN - 0305-1048
VL - 46
SP - 2585
EP - 2599
JO - Nucleic acids research
JF - Nucleic acids research
IS - 5
ER -