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This \u2018\u03c3-cycle\u2019, in which \u03c3 binds to RNA polymerase (RNAP) to initiate transcription and is released during transcription elongation, is thought to be an essential step for \u03c3-switching. Studies in Escherichia coli provide evidence that \u03c370 is stochastically released from the elongation complex. This \u2018\u03c3-cycle\u2019 became a general model for all \u03c3 factors of all bacteria. Here, using three distinct groups of \u03c3 factors in Mycobacterium tuberculosis, we show that although a significant fraction of \u03c3A and \u03c3E are stochastically or immediately released from RNAP during the transition from transcription initiation to elongation, most of \u03c3F are retained. We also show that NusA facilitates \u03c3A release from elongation complexes at specific genes but does not affect the release of \u03c3E and \u03c3F. Our results further indicate that \u03c3F remains bound at the elongation complex despite the displacement of \u03c34, as \u03c32 and \u03c33 remain associated with RNAP. Our study demonstrates that \u03c3-release is not a universal phenomenon\u2014the release or retention of \u03c3 factor depends on its domain architecture.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1459","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T12:48:35Z","timestamp":1766666915000},"source":"Crossref","is-referenced-by-count":2,"title":["Differential association of primary and alternative \u03c3 factors with RNA polymerase of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    during transcription elongation"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1569-7491","authenticated-orcid":false,"given":"Nilanjana","family":"Hazra","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, Bose Institute , EN 80, Sector V, Bidhan Nagar, Kolkata 700091 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-5908","authenticated-orcid":false,"given":"Jayanta","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Bose Institute , EN 80, Sector V, Bidhan Nagar, Kolkata 700091 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"2026010810164797000_B1","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1146\/annurev.micro.54.1.499","article-title":"Functional modulation of Escherichia coli RNA polymerase","volume":"54","author":"Ishihama","year":"2000","journal-title":"Annu Rev Microbiol"},{"key":"2026010810164797000_B2","doi-asserted-by":"publisher","first-page":"5447","DOI":"10.1128\/jb.178.18.5447-5451.1996","article-title":"Regulation of RNA polymerase sigma subunit synthesis in Escherichia coli: intracellular levels of four species of sigma subunit under various growth conditions","volume":"178","author":"Jishage","year":"1996","journal-title":"J Bacteriol"},{"key":"2026010810164797000_B3","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1039\/b904955j","article-title":"A global view of Escherichia coli Rsd protein and its interactions","volume":"5","author":"Piper","year":"2009","journal-title":"Mol Biosyst"},{"key":"2026010810164797000_B4","first-page":"1164","article-title":"Escherichia coli RNA polymerase: purification, subunit structure, and factor requirements","volume":"29","author":"Burgess","year":"1970","journal-title":"Fed Proc"},{"key":"2026010810164797000_B5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/221043a0","article-title":"Factor stimulating transcription by RNA polymerase","volume":"221","author":"Burgess","year":"1969","journal-title":"Nature"},{"key":"2026010810164797000_B6","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/0022-2836(91)90015-X","article-title":"Escherichia coli sigma 70 and NusA proteins. 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