A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration

Adrien Chauvier, Shiba S. Dandpat, Rosa Romero and Nils G. Walter ()
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Adrien Chauvier: University of Michigan
Shiba S. Dandpat: University of Michigan
Rosa Romero: University of Michigan
Nils G. Walter: University of Michigan

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches – like most structured RNAs – are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single-molecule and bulk approaches, we discover how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the representative Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.

Date: 2024
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DOI: 10.1038/s41467-024-48409-8

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