RNA folding kinetics control riboswitch sensitivity in vivo.

ABSTRACT: Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC₅₀) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contexts with different sensitivity demands. Here we uncover roles by which RNA folding dynamics control riboswitch sensitivity in cells. By investigating the Clostridium beijerinckii pfl ZTP riboswitch, we identify multiple mechanistic routes of altering expression platform sequence and structure to slow RNA folding, all of which enhance riboswitch sensitivity. Applying these methods to riboswitches with diverse aptamer architectures and regulatory mechanisms demonstrates the generality of our find

SUBMITTER: Bushhouse DZ 

PROVIDER: S-EPMC11754884 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature