Publication Title

Nucleic Acids Research

Document Type

Article

Department or Program

Chemistry

Second Department or Program

Biochemistry

Publication Date

5-22-2024

Abstract

The σ54-σS sigma factor cascade plays a central role in regulating differential gene expression during the enzootic cycle of Borreliella burgdorferi, the Lyme disease pathogen. In this pathway, the primary transcription of rpoS (which encodes σS) is under the control of σ54 which is activated by a bacterial enhancer-binding protein (EBP), Rrp2. The σ54-dependent activation in B. burgdorferi has long been thought to be unique, requiring an additional factor, BosR, a homologue of classical Fur/PerR repressor/activator. However, how BosR is involved in this σ54-dependent activation remains unclear and perplexing. In this study, we demonstrate that BosR does not function as a regulator for rpoS transcriptional activation. Instead, it functions as a novel RNA-binding protein that governs the turnover rate of rpoS mRNA. We further show that BosR directly binds to the 5 untranslated region (UTR) of rpoS mRNA, and the binding region overlaps with a region required for rpoS mRNA degradation. Mutations within this 5 UTR region result in BosR-independent RpoS production. Collectively, these results uncover a novel role of Fur/PerR family regulators as RNA-binding proteins and redefine the paradigm of the σ54–σS pathway in B. burgdorferi.

Comments

Original version is available from the publisher at: https://doi.org/10.1093/nar/gkae114

PubMed ID

38366569

Copyright Note

Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.

Required Publisher's Statement

This is an Open Access article distributed under the terms of the CC-BY License, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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