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In this pathway, the primary transcription of rpoS (which encodes \u03c3S) is under the control of \u03c354 which is activated by a bacterial enhancer-binding protein (EBP), Rrp2. The \u03c354-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 \u03c354-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\u2032 untranslated region (UTR) of rpoS mRNA, and the binding region overlaps with a region required for rpoS mRNA degradation. Mutations within this 5\u2032UTR 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 \u03c354\u2013\u03c3S pathway in B. burgdorferi.<\/jats:p>","DOI":"10.1093\/nar\/gkae114","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T06:03:35Z","timestamp":1708149815000},"page":"5320-5335","source":"Crossref","is-referenced-by-count":13,"title":["A Fur family protein BosR is a novel RNA-binding protein that controls <i>rpoS<\/i> RNA stability in the Lyme disease pathogen"],"prefix":"10.1093","volume":"52","author":[{"given":"Sajith","family":"Raghunandanan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis , IN\u00a046202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Priya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis , IN\u00a046202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuad","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis , IN\u00a046202, USA"},{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University , Riyadh\u00a0 12372 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan C","family":"Lybecker","sequence":"additional","affiliation":[{"name":"Bacterial Diseases Branch, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Center for Disease Control and Prevention , Fort Collins , CO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula\u00a0Jean","family":"Schlax","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Bates College , Lewiston , ME , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-3167","authenticated-orcid":false,"given":"X\u00a0Frank","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis , IN\u00a046202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"2024052209490699700_B1","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"Steere","year":"2016","journal-title":"Nat. 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