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A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
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...
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Published in: | Nature communications 2024-05, Vol.15 (1), p.3955-18, Article 3955 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | 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
2+
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.
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from
L. lactis
. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-024-48409-8 |