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Many environmental and regulatory signals control SPI1 gene expression, but in most cases, the molecular mechanisms remain unclear. Many regulatory signals control SPI1 at a post-transcriptional level, and we have identified a number of small RNAs (sRNAs) that control the SPI1 regulatory circuit. The transcriptional regulator HilA activates the expression of the genes encoding the SPI1 T3SS structural and primary effector proteins. Transcription of\n              <jats:italic>hilA<\/jats:italic>\n              is controlled by the AraC-like proteins HilD, HilC, and RtsA. The\n              <jats:italic>hilA<\/jats:italic>\n              mRNA 5\u2032 untranslated region (UTR) is ~350 nucleotides in length and binds the RNA chaperone Hfq, suggesting it is a likely target for sRNA-mediated regulation. We used rGRIL-seq (reverse global sRNA target identification by ligation and sequencing) to identify sRNAs that bind to the\n              <jats:italic>hilA<\/jats:italic>\n              5\u2032 UTR. The rGRIL-seq data, along with genetic analyses, demonstrate the SPI1-encoded sRNA\n              <jats:underline>inv<\/jats:underline>\n              asion gene-associated\n              <jats:underline>R<\/jats:underline>\n              NA (InvR) base pairs at a site overlapping the\n              <jats:italic>hilA<\/jats:italic>\n              ribosome binding site. HilD and HilC activate both\n              <jats:italic>invR<\/jats:italic>\n              and\n              <jats:italic>hilA<\/jats:italic>\n              . InvR, in turn, negatively regulates the translation of the\n              <jats:italic>hilA<\/jats:italic>\n              mRNA. Thus, the SPI1-encoded sRNA InvR acts as a negative feedback regulator of SPI1 expression. Our results suggest that InvR acts to fine-tune SPI1 expression and prevents overactivation of\n              <jats:italic>hilA<\/jats:italic>\n              expression, highlighting the complexity of sRNA regulatory inputs controlling SPI1 and\n              <jats:italic>Salmonella<\/jats:italic>\n              virulence.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Salmonella<\/jats:italic>\n              Typhimurium infections pose a significant public health concern, leading to illnesses that range from mild gastroenteritis to severe systemic infection. Infection requires a complex apparatus that the bacterium uses to invade the intestinal epithelium. Understanding how\n              <jats:italic>Salmonella<\/jats:italic>\n              regulates this system is essential for addressing these infections effectively. Here, we show that the small RNA (sRNA) InvR imposes a negative feedback regulation on the expression of the invasion system. This work underscores the role of sRNAs in\n              <jats:italic>Salmonella<\/jats:italic>\n              's complex regulatory network, offering new insights into how these molecules contribute to bacterial adaptation and pathogenesis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jb.00491-24","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T14:00:52Z","timestamp":1740664852000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["The\n            <i>Salmonella<\/i>\n            pathogenicity island 1-encoded small RNA InvR mediates post-transcriptional feedback control of the activator HilA in\n            <i>Salmonella<\/i>"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3932-7774","authenticated-orcid":false,"given":"Yutong","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungsub","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatih","family":"Cakar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yekaterina A.","family":"Golubeva","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-9702","authenticated-orcid":true,"given":"James M.","family":"Slauch","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-5532","authenticated-orcid":true,"given":"Carin K.","family":"Vanderpool","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.08.008"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/650733"},{"key":"e_1_3_4_4_2","first-page":"85","article-title":"Genetic and environmental control of Salmonella invasion","volume":"43","author":"Altier C","year":"2005","unstructured":"Altier C. 2005. 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