{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:33:40Z","timestamp":1789734820839,"version":"4.0.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T00:00:00Z","timestamp":1478563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T00:00:00Z","timestamp":1483056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,12,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            VirF, an AraC-like activator, is required to trigger a regulatory cascade that initiates the invasive program of\n            <jats:italic>Shigella<\/jats:italic>\n            spp., the etiological agents of bacillary dysentery in humans. VirF expression is activated upon entry into the host and depends on many environmental signals. Here, we show that the\n            <jats:italic>virF<\/jats:italic>\n            mRNA is translated into two proteins, the major form, VirF\n            <jats:sub>30<\/jats:sub>\n            (30\u00a0kDa), and the shorter VirF\n            <jats:sub>21<\/jats:sub>\n            (21\u00a0kDa), lacking the N-terminal segment. By site-specific mutagenesis and toeprint analysis, we identified the translation start sites of VirF\n            <jats:sub>30<\/jats:sub>\n            and VirF\n            <jats:sub>21<\/jats:sub>\n            and showed that the two different forms of VirF arise from differential translation. Interestingly,\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            translation experiments showed that VirF\n            <jats:sub>21<\/jats:sub>\n            is also translated from a leaderless mRNA (llmRNA) whose 5\u2032 end is at position +309\/+310, only 1 or 2 nucleotides upstream of the ATG84 start codon of VirF\n            <jats:sub>21<\/jats:sub>\n            . The llmRNA is transcribed from a gene-internal promoter, which we identified here. Functional analysis revealed that while VirF\n            <jats:sub>30<\/jats:sub>\n            is responsible for activation of the virulence system, VirF\n            <jats:sub>21<\/jats:sub>\n            negatively autoregulates\n            <jats:italic>virF<\/jats:italic>\n            expression itself. Since VirF\n            <jats:sub>21<\/jats:sub>\n            modulates the intracellular VirF levels, this suggests that transcription of the llmRNA might occur when the onset of the virulence program is not required. We speculate that environmental cues, like stress conditions, may promote changes in\n            <jats:italic>virF<\/jats:italic>\n            mRNA transcription and preferential translation of llmRNA.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:italic>Shigella<\/jats:italic>\n            spp. are a major cause of dysentery in humans. In bacteria of this genus, the activation of the invasive program involves a multitude of signals that act on all layers of the gene regulatory hierarchy. By controlling the essential genes for host cell invasion, VirF is the key regulator of the switch from the noninvasive to the invasive phenotype. Here, we show that the\n            <jats:italic>Shigella virF<\/jats:italic>\n            gene encodes two proteins of different sizes, VirF\n            <jats:sub>30<\/jats:sub>\n            and VirF\n            <jats:sub>21<\/jats:sub>\n            , that are functionally distinct. The major form, VirF\n            <jats:sub>30<\/jats:sub>\n            , activates the genes necessary for virulence, whereas the minor VirF\n            <jats:sub>21<\/jats:sub>\n            , which shares the C-terminal two-thirds of VirF\n            <jats:sub>30<\/jats:sub>\n            , negatively autoregulates\n            <jats:italic>virF<\/jats:italic>\n            expression itself. VirF\n            <jats:sub>21<\/jats:sub>\n            is transcribed from a newly identified gene-internal promoter and, moreover, is translated from an unusual leaderless mRNA. The identification of a new player in regulation adds complexity to the regulation of the\n            <jats:italic>Shigella<\/jats:italic>\n            invasive process and may help development of new therapies for shigellosis.\n          <\/jats:p>","DOI":"10.1128\/mbio.01860-16","type":"journal-article","created":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T11:00:34Z","timestamp":1478689234000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["One Gene and Two Proteins: a Leaderless mRNA Supports the Translation of a Shorter Form of the\n            <i>Shigella<\/i>\n            VirF Regulator"],"prefix":"10.1128","volume":"7","author":[{"given":"Maria Letizia","family":"Di Martino","sequence":"first","affiliation":[{"name":"Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biology and Biotechnology C. Darwin, Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Romilly","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Gerhart H.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Colonna","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biology and Biotechnology C. 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