A Nascent Riboswitch Helix Orchestrates Robust Transcriptional Regulation Through Signal Integration

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 10

PMID 38729929

Authors

Adrien Chauvier

Shiba S Dandpat

Rosa Romero

Nils G Walter

Affiliations

Soon will be listed here.

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 Mn 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.

Citing Articles

Opportunities for Riboswitch Inhibition by Targeting Co-Transcriptional RNA Folding Events.

Stephen C, Palmer D, Mishanina T Int J Mol Sci. 2024; 25(19).

PMID: 39408823 PMC: 11476745. DOI: 10.3390/ijms251910495.

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