Structural analysis of regulatory RNAs: Hfq-mediated gene regulation by small trans-acting RNAs

小反式作用RNA（Small trans-acting RNAs，sRNA）在原核生物的转录后基因调控中起着重要作用。sRNA由六聚体Sm样蛋白Hfq辅助，Hfq在体内稳定它们，促进与其mRNA靶点的相互作用并触发下游过程。这是如何机械地实现的在很大程度上是模糊的。我们将进行重构分析，目的是获得Hfq与sRNA或sRNA/mRNA杂交体复合的晶体结构。这些结构应该提供至关重要的机制的见解，并应揭示与真核microRNA途径的概念相似之处，以及与最近确定的真核Sm-环与U1 snRNA复合的晶体结构的结构相似之处。

Small trans-acting RNAs (sRNA) play a major role in the post-transcriptional gene regulation in prokaryotes. sRNAs are assisted by the hexameric Sm-like protein Hfq that stabilizes them in vivo, promotes the interaction with their mRNA targets and triggers downstream processes. How this is achieved mechanistically is largely obscure. We will do reconstitution analyses and aim to obtain crystal structures of Hfq in complex with an sRNA or with an sRNA/mRNA hybrid. These structures should provide crucial mechanistic insight and should reveal conceptual parallels with the eukaryotic microRNA pathway as well as structural parallels with a recently determined crystal structure of a eukaryotic Sm-ring complexed to the U1snRNA.