ABSTRACT

Recent studies have established that a major class of small RNAs (sRNAs) bind to an RNA chaperon Hfq and act by imperfect base pairing to regulate the translation and stability of target mRNAs under specific physiological conditions in Escherichia coli. I will discuss here how the posttranscriptional regulation of gene expression mediated by Hfq-binding sRNAs has been discovered and what we have learned about their physiological roles and their mechanisms of action by focusing on two

Overview .................................................................................................................. 57 4.1 Introduction .................................................................................................... 58 4.2 The Beginning ................................................................................................ 58 4.3 Hfq-Binding sRNAs and Target mRNAs ....................................................... 59 4.4 Discovery of MicF ..........................................................................................60 4.5 More Small RNAs before Systematic Searches ............................................. 62 4.6 Genome-Wide Searches of sRNAs ................................................................. 63 4.7 Function of Spot42 RNA ................................................................................64 4.8 RyhB and Iron Metabolism ............................................................................65 4.9 Coupled Degradation of sRNAs and mRNA Targets .....................................65 4.10 SgrS and Glucose Phosphate Stress ................................................................66 4.11 Ribonucleoprotein Complex Consisting of an sRNA, Hfq, and RNase E ...... 67 4.12 Implication of Membrane Localization of Target mRNAs ............................ 67 4.13 Translational Repression Is the Primary Event for Gene Silencing ...............68 4.14 Base-Pairing Requirement and Role of Hfq in SgrS-ptsG System ................68 4.15 sRNAs and Outer Membrane Proteins ...........................................................69 4.16 Conclusions and Perspectives ......................................................................... 70 Acknowledgment ..................................................................................................... 72 References ................................................................................................................ 72

stress-induced sRNAs: SgrS and RyhB. These sRNAs form a specific ribonucleoprotein complex with RNase E through Hfq, resulting in translation inhibition and RNase E-dependent degradation of target mRNAs. Translation inhibition is the primary event for gene silencing. Degradation of both target mRNAs and sRNAs occurs simultaneously. The crucial base pairs for the action of SgrS are confined to the 6-nt region, overlapping the Shine-Dalgarno sequence of the target mRNA. Hfq accelerates the rate of duplex formation between SgrS and the target mRNA. Membrane localization of target mRNA contributes to efficient SgrS action by competing with ribosome loading.