Abstract

Transcriptional riboswitches involve RNA aptamers that are typically found in the 5′ untranslated regions (UTRs) of bacterial mRNAs and form alternative secondary structures upon binding to cognate ligands. Alteration of the riboswitch's secondary structure results in perturbations of an adjacent expression platform that controls transcription elongation and termination, thus turning downstream gene expression “on” or “off.” Riboswitch ligands are typically small metabolites, divalent cations, anions, signaling molecules, or other RNAs, and can be part of larger signaling cascades. The interconnectedness of ligand binding, RNA folding, RNA transcription, and gene expression empowers riboswitches to integrate cellular processes and environmental conditions across multiple timescales. For a successful response to an environmental cue that may determine a bacterium's chance of survival, a coordinated coupling of timescales from microseconds to minutes must be achieved. This review focuses on recent advances in our understanding of how riboswitches affect such critical gene expression control across time.

Highlights

  • Over the past several decades, RNA has emerged as a key player beyond a “message” between DNA and protein

  • When Salmonella is deficient in Mn2+, transcription elongation of the mntH gene becomes permissive, FIGURE 1 | Recent advances in single-molecule techniques have allowed for the study of transcriptional riboswitches on a variety of biologically relevant timescales: (A) Transcriptional riboswitches, such as the Mn2+ riboswitch, consist of a ligand binding, or “aptamer” region that controls the shape of the “expression platform” region to control transcription termination by the transcribing RNA polymerase (RNAP). (B) Riboswitch mediated upregulation of a gene happens co-transcriptionally where events like RNA folding leading to aptamer formation occur at a timescale of micro-second to milliseconds

  • Established methods including X-ray crystallography together with more recent advances in high-resolution cryo-electron microscopy (cryo-EM) have provided snapshots of RNA structures that have aided in identifying ligand binding sites and RNA structures (Garst and Batey, 2009; Frank, 2017; Zhang et al, 2019)

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Summary

Introduction

Over the past several decades, RNA has emerged as a key player beyond a “message” between DNA and protein. This review primarily focuses on the function of riboswitches involved in transcription regulation, encompassing events on timescales ranging from ligand binding to RNA folding, RNA transcription, and far-reaching cellular gene expression control.

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