Chaperone modulation and the structural basis for sRNA recognition by the conserved ribonuclease YicC

The broadly conserved bacterial endoribonuclease YicC represents a widespread but enigmatic family of RNA processing enzymes with poorly defined substrate selectivity. Here, we show that Escherichia coli YicC displays a distinct selectivity, cleaving small regulatory RNAs (sRNAs) such as RyhB and RprA but not when they are in complexes with cognate mRNA targets or RNA sponges. Furthermore, we demonstrate that RyhB processing is modulated, but not abolished, by the RNA chaperone Hfq. Our cryo-EM structures of E. coli YicC in apo form and in complexes with substrate and non-substrate RNA species capture marked quaternary and tertiary structural switches triggered by sRNA stem-loop binding that engulf and ratchet the RNA into an internal catalytic channel. Structural comparison of cleavable (RyhB) and non-cleavable (MicA) sRNA-bound complexes reveal a near-identical ground-state binding mode, proving that cavity docking is sequence-tolerant and decoupled from catalytic execution. Together, our findings suggest that YicC may be a state-selective endoribonuclease and reveal a framework for selective RNA clearance in bacterial post-transcriptional regulation.