Co-transcriptional folding orchestrates sequential multi-effector sensing by a glycine tandem riboswitch.

ABSTRACT: Riboswitches are non-coding RNA motifs that regulate gene expression in response to ligand binding. The glycine tandem riboswitch (GTR) is notable because it comprises two distinct glycine aptamers that interact extensively. These inter-aptamer contacts drive conformational changes in the downstream expression platform to control gene expression. Despite extensive studies, the role of glycine and RNA folding pathways in co-transcriptional regulation remains unclear. Here, we integrate single-molecule kinetic analysis, co-transcriptional RNA structure probing, and computational modeling to reveal that the GTR processes multiple molecular inputs sequentially, guided by polymerase pausing. Our findings elucidate its stepwise 5'-to-3' folding pathway and demonstrate how sequential glycine bind

SUBMITTER: Romero RA 

PROVIDER: S-EPMC12154632 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature