{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:16:12Z","timestamp":1773926172847,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>POLR1D is a subunit of RNA Polymerases I and III, which synthesize ribosomal RNAs. Dysregulation of these polymerases cause several types of diseases, including ribosomopathies. The craniofacial disorder Treacher Collins Syndrome (TCS) is a ribosomopathy caused by mutations in several subunits of RNA Polymerase I, including POLR1D. Here, we characterized the effect of a missense mutation in POLR1D and RNAi knockdown\u00a0of <jats:italic>POLR1D<\/jats:italic> on <jats:italic>Drosophila<\/jats:italic> development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that a missense mutation in <jats:italic>Drosophila<\/jats:italic> POLR1D (G30R) reduced larval rRNA levels, slowed larval growth, and arrested larval development. Remarkably, the G30R substitution is at an orthologous glycine in POLR1D that is mutated in a TCS patient (G52E). We showed that the G52E mutation in human POLR1D, and the comparable substitution (G30E) in <jats:italic>Drosophila<\/jats:italic> POLR1D, reduced their ability to heterodimerize with POLR1C <jats:italic>in vitro<\/jats:italic>. We also found that POLR1D is required early in the development of <jats:italic>Drosophila<\/jats:italic> neural cells. Furthermore, an RNAi screen revealed that POLR1D is also required for development of non\u2010neural <jats:italic>Drosophila<\/jats:italic> cells, suggesting the possibility of defects in other cell types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results establish a role for POLR1D in <jats:italic>Drosophila<\/jats:italic> development, and present <jats:italic>Drosophila<\/jats:italic> as an attractive model to evaluate the molecular defects of TCS mutations in POLR1D.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.505","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T02:33:41Z","timestamp":1654223621000},"page":"1780-1797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A clinically\u2010relevant residue of POLR1D is required for <i>Drosophila<\/i> development"],"prefix":"10.1002","volume":"251","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-7676","authenticated-orcid":false,"given":"Ryan J.","family":"Palumbo","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alana E.","family":"Belkevich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haleigh G.","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1302","authenticated-orcid":false,"given":"Bruce A.","family":"Knutson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology SUNY Upstate Medical University  Syracuse New York 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