{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T07:44:57Z","timestamp":1784447097950,"version":"3.55.0"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"27","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/S\/17\/1\/503071"],"award-info":[{"award-number":["IA\/S\/17\/1\/503071"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"DST | Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2016\/005296"],"award-info":[{"award-number":["EMR\/2016\/005296"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/IC-06\/003\/91"],"award-info":[{"award-number":["BT\/IC-06\/003\/91"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:p>\n                    Transcriptional adaptation drives the host responses to\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    ) infection. However,\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    alters host RNA splicing to quench host antibacterial responses, the mechanism for which remains unknown. Here, we report a mechanism whereby a secreted\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    protein interferes with the biogenesis of key spliceosomal components. A high-throughput yeast-2-hybrid screen identified several\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    -secreted proteins interacting with the host RNA splicing factors (SFs). Through custom-designed in-cell assays, we show that one of those proteins, Rv1435c\/hsr1 (host splicing regulator 1), targets specific exon-skipping events. The\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    Rv14345c\/hsr1 facilitates direct interaction between\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    phagosomes and U5 snRNA and SNRPF, key components of the snRNPs. Genetic deletion of Rv1435c\/hsr1 reverses the specific exon-skipping events caused by WT\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    infection. The \u0394\n                    <jats:italic toggle=\"yes\">hsr1<\/jats:italic>\n                    strain shows compromised growth during ex vivo infection in macrophages and in vivo infection in mice. Tissue sections from the WT\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">\u0394hsr1<\/jats:italic>\n                    -infected mice showed significant hsr1-dependent SNRPF staining, a phenomenon also noted in the human intestinal tuberculosis (ITB) biopsies. Thus, hsr1 is a virulence factor that disrupts host snRNP biogenesis for pathogenesis. The splicing regulators from the host and pathogen are novel targets for antituberculosis therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2423349122","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:41:21Z","timestamp":1751463681000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["A\n                    <i>Mycobacterium tuberculosis<\/i>\n                    secreted virulence factor Rv1435c\/hsr1 disrupts host snRNP biogenesis"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9011-8242","authenticated-orcid":false,"given":"Komal","family":"Chauhan","sequence":"first","affiliation":[{"name":"Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg","place":["New Delhi, 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Chauhan Regulation of host RNA splicing in Mycobacterium tuberculosis infected macrophages. ProteomeXchange. https:\/\/ftp.pride.ebi.ac.uk\/pride\/data\/archive\/2025\/06\/PXD039671\/. 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