Substrate induced activation in the conserved ribonuclease YicC

YicC is a conserved protein, recently discovered to have hydrolytic endoribonuclease activity, with a phylogenetic distribution implicating an ancestry deeper than that for most extant ribonucleases central to RNA metabolism. We present evidence that Escherichia coli YicC can cleave the small regulatory RNAs (sRNAs), RyhB and RprA, even when they are sequestered in otherwise protective complexes with the RNA chaperone Hfq. Nonetheless, YicC activity is markedly diminished when RyhB and other sRNAs are paired with cognate mRNA. Our cryoEM structures of catalytically inactive YicC in complex with RyhB and in the apo state reveal quaternary and tertiary structural switches, triggered by substrate engagement, that engulf and ratchet a stem loop element of the sRNA into an internal channel, where metal-assisted hydrolytic action occurs. Based on these findings, we propose that the enzyme favours specific stem-loop structures and may discriminate between pools of active, target-engaged sRNAs and those that are inactive. The mechanism for substrate-triggered conformational switching could represent an ancient strategy for selective RNA degradation.