RNAs actively cycle on the Sm-like protein Hfq

Aurélie Fender; Johan Elf; Kornelia Hampel; Bastian Zimmermann; E. Gerhart H. Wagner

doi:10.1101/gad.591310

RNAs actively cycle on the Sm-like protein Hfq

¹Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, SE-75124 Uppsala, Sweden;
²Science for Life Laboratory, SE-75124 Uppsala, Sweden;
³Biaffin GmbH & Co. KG, D-34132 Kassel, Germany

Abstract

Hfq, a protein required for small RNA (sRNA)-mediated regulation in bacteria, binds RNA with low-nanomolar K_d values and long half-lives of complexes (>100 min). This cannot be reconciled with the 1- 2-min response time of regulation in vivo. We show that RNAs displace each other on Hfq on a short time scale by RNA concentration-driven (active) cycling. Already at submicromolar concentrations of competitor RNA, half-lives of RNA–Hfq complexes are ≈1 min. We propose that competitor RNA associates transiently with RNA–Hfq complexes, RNAs exchange binding sites, and one of the RNAs eventually dissociates. This solves the “strong binding–high turnover” paradox and permits efficient use of the Hfq pool.