{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:06:08Z","timestamp":1768503968127,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,2]]},"group-title":"Microbiology","reference-count":29,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,2]]},"abstract":"<jats:p>\n                  Recombination-promoting nuclease (Rpn) proteins are broadly distributed across bacterial phyla, yet their functions remain unclear. Here we report these proteins are new toxin-antitoxin systems, comprised of genes-within-genes, that combat phage infection. We show the small, highly variable Rpn\n                  <jats:italic>C<\/jats:italic>\n                  -terminal domains (Rpn\n                  <jats:sub>S<\/jats:sub>\n                  ), which are translated separately from the full-length proteins (Rpn\n                  <jats:sub>L<\/jats:sub>\n                  ), directly block the activities of the toxic full-length proteins. The crystal structure of RpnA\n                  <jats:sub>S<\/jats:sub>\n                  revealed a dimerization interface encompassing a helix that can have four amino acid repeats whose number varies widely among strains of the same species. Consistent with strong selection for the variation, we document plasmid-encoded RpnP2\n                  <jats:sub>L<\/jats:sub>\n                  protects\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  against certain phages. We propose many more intragenic-encoded proteins that serve regulatory roles remain to be discovered in all organisms.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Here we document the function of small genes-within-genes, showing they encode antitoxin proteins that block the functions of the toxic DNA endonuclease proteins encoded by the longer\n                    <jats:italic>rpn<\/jats:italic>\n                    genes. Intriguingly, a sequence present in both long and short protein shows extensive variation in the number of four amino acid repeats. Consistent with a strong selection for the variation, we provide evidence that the Rpn proteins represent a phage defense system.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.02.539157","type":"posted-content","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:05:21Z","timestamp":1683072321000},"source":"Crossref","is-referenced-by-count":0,"title":["Toxic anti-phage defense proteins inhibited by intragenic antitoxin proteins"],"prefix":"10.64898","author":[{"given":"Aoshu","family":"Zhong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-8284","authenticated-orcid":false,"given":"Xiaofang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison B.","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Klier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella I. C.","family":"Teodoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Dyda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Laub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6698-1241","authenticated-orcid":false,"given":"Gisela","family":"Storz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023050509501303000_2023.05.02.539157v1.1","doi-asserted-by":"crossref","unstructured":"S. Meydan , N. V\u00e1zquez-Laslop , A. S. Mankin , Genes within genes in bacterial genomes. Microbiol. 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