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We report discordance of changes in nascent transcript and total nuclear RNA abundance for the transcription factors STAT1 and IRF1, together with lack of effect on their RNA half-lives, in human THP-1 cells infected with M. tuberculosis and stimulated with IFN-\u03b3. The results indicate that negative postinitiation regulation of mRNA biogenesis limits the expression of these factors, which mediate host defense against M. tuberculosis through the cellular response to IFN-\u03b3. Consistent with the results for STAT1 and IRF1, transcriptome analysis reveals downregulation of postinitiation mRNA biogenesis processes and pathways by infection, with and without IFN-\u03b3 stimulation. Clinical relevance for regulation of postinitiation mRNA biogenesis is demonstrated by studies of donor samples showing that postinitiation mRNA biogenesis pathways are repressed in latent tuberculosis infection compared with cured disease and in active tuberculosis compared with ongoing treatment or with latent tuberculosis. For active disease and latent infection donors from two populations (London, U.K., and The Gambia), each analyzed using a different platform, pathway-related gene expression differences were highly correlated, demonstrating substantial specificity in the effect. Collectively, the molecular and bioinformatic analyses point toward downregulation of postinitiation mRNA biogenesis pathways as a means by which M. tuberculosis infection limits expression of immunologically essential transcription factors. Thus, negative regulation of postinitiation mRNA biogenesis can constrain the macrophage response to infection and overall host defense against tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1202185","type":"journal-article","created":{"date-parts":[[2013,2,2]],"date-time":"2013-02-02T02:58:25Z","timestamp":1359773905000},"page":"2747-2755","source":"Crossref","is-referenced-by-count":3,"title":["Evidence for Postinitiation Regulation of mRNA Biogenesis in Tuberculosis"],"prefix":"10.1093","volume":"190","author":[{"given":"Hugh","family":"Salamon","sequence":"first","affiliation":[{"name":"Knowledge Synthesis, Inc. , Berkeley, CA 94716"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaming","family":"Qiao","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff C","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, New Jersey Institute of Technology , Newark, NJ 07102"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken D","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Knowledge Synthesis, Inc. , Berkeley, CA 94716"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Soteropoulos","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Weiden","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Laura","family":"Gennaro","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"},{"name":"Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Pine","sequence":"additional","affiliation":[{"name":"Public Health Research Institute Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"},{"name":"Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"2025032406433053000_r1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1001\/archinte.163.9.1009","article-title":"The growing burden of tuberculosis: global trends and interactions with the HIV epidemic","volume":"163","author":"Corbett","year":"2003","journal-title":"Arch. 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