RT Journal Article
SR Electronic
T1 A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 521930
DO 10.1101/521930
A1 Eric J. Strobel
A1 Luyi Cheng
A1 Katherine E. Berman
A1 Paul D. Carlson
A1 Julius B. Lucks
YR 2019
UL http://biorxiv.org/content/early/2019/02/12/521930.abstract
AB Cotranscriptional folding is an obligate step of RNA biogenesis that can guide RNA structure and function by forming transient intermediate folds. This is especially true for transcriptional riboswitches in the which the formation of ligand-dependent structures during transcription regulates downstream gene expression. However, the intermediate structures that comprise cotranscriptional RNA folding pathways and the mechanisms that enable transit between them remain largely unknown. Here we determine the series of cotranscriptional folds and rearrangements that mediate antitermination by the Clostridium beijerinckii pfl riboswitch in response to the purine biosynthetic intermediate ZMP. We uncover sequence and structural determinants that modulate a regulatory RNA strand displacement reaction and identify biases within natural ZTP riboswitch sequences that promote on-pathway folding. Our findings establish a mechanism for ZTP riboswitch antitermination and suggest general strategies by which nascent RNA molecules can navigate cotranscriptional folding pathways efficiently.