{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:54:47Z","timestamp":1790916887606,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Centre \u201cKurchatov Institute\u201d","id":[{"id":"https:\/\/ror.org\/02n85j827","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02n85j827","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Russian Foundation for Basic Research","award":["#18-04-01127-a"],"award-info":[{"award-number":["#18-04-01127-a"]}],"id":[{"id":"https:\/\/ror.org\/02mh1ke95","id-type":"ROR","asserted-by":"crossref"}]},{"award":["#18-04-01127-a"],"award-info":[{"award-number":["#18-04-01127-a"]}],"id":[{"id":"https:\/\/ror.org\/02mh1ke95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Revealing gene expression patterns is essential for comprehending the genetic control of complex traits like lifespan. Analyzing structural variation in gene regulatory regions within natural populations is a promising approach in functional genetics, allowing us to identify regulatory sites that influence transcription and phenotype in vivo. We describe the structural variability of the 5\u2032 regulatory region of the shuttle craft (stc) gene in the Alexandrov population (Russia) of Drosophila melanogaster, encoding a transcription factor homologous to human NF-X1. We evaluated the association of frequently occurring polymorphisms with fly lifespan from inbred lines sampled in 2010, 2011, and 2014. Two polymorphisms in the stc 5\u2032 regulatory region exhibit strong associations with both lifespan and embryonic stc transcript levels. Their role in expression regulation was evaluated via reporter gene assays conducted in S2 Drosophila cell culture. The \u2018C\u2019 allele at one polymorphic site and \u2018T\u2019 at the other are associated with increased longevity and decreased embryonic stc transcription, reaffirming the link between gene expression and lifespan we previously established. Furthermore, comparing stc 5\u2032 regulatory region variability across Alexandrov, European and African populations suggests that the macro-geographic distribution of these longevity-associated variants is consistent with a potential role in latitudinal or climatic adaptation.<\/jats:p>","DOI":"10.3390\/ijms27188343","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:23:56Z","timestamp":1790864636000},"page":"8343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1473-4470","authenticated-orcid":false,"given":"Alexander V.","family":"Symonenko","sequence":"first","affiliation":[{"name":"National Research Centre \u201cKurchatov Institute\u201d, 2 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Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin St., 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2665-7137","authenticated-orcid":false,"given":"Elena A.","family":"Mikhaleva","sequence":"additional","affiliation":[{"name":"National Research Centre \u201cKurchatov Institute\u201d, 2 Kurchatov Sq., 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Vladimir E.","family":"Alatortsev","sequence":"additional","affiliation":[{"name":"National Research Centre \u201cKurchatov Institute\u201d, 2 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