{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:51:11Z","timestamp":1787824271124,"version":"build-2784847793"},"reference-count":43,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS102538"],"award-info":[{"award-number":["R01NS102538"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2018257410"],"award-info":[{"award-number":["2018257410"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Disruption of the minor spliceosome due to mutations in RNU4ATAC is linked to primordial dwarfism in microcephalic osteodysplastic primordial dwarfism type 1, Roifman syndrome, and Lowry-Wood syndrome. Similarly, primordial dwarfism in domesticated animals is linked to positive selection in minor spliceosome components. Despite being vital for limb development and size regulation, its role remains unexplored. Here we disrupt minor spliceosome function in the developing mouse limb by ablating one of its essential components, U11 small nuclear RNA, which resulted in micromelia. Notably, earlier loss of U11 corresponded to increased severity. We find that limb size is reduced due to elevated minor intron retention in minor intron-containing genes that regulate cell cycle. As a result, limb progenitor cells experience delayed prometaphase to metaphase transition and prolonged S-phase. Moreover, we observed death of rapidly dividing, distally located progenitors. Despite cell cycle defects and cell death, the spatial expression of key limb patterning genes was maintained. Overall, we show that the minor spliceosome is required for limb development via size control potentially shared in disease and domestication.<\/jats:p>","DOI":"10.1242\/dev.190967","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T19:25:21Z","timestamp":1594754721000},"source":"Crossref","is-referenced-by-count":10,"title":["Loss of U11 small nuclear RNA in the developing mouse limb results in micromelia"],"prefix":"10.1242","author":[{"given":"Kyle D.","family":"Drake","sequence":"first","affiliation":[{"name":"Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lemoine","sequence":"additional","affiliation":[{"name":"Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA"},{"name":"College of Medicine, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela S.","family":"Aquino","sequence":"additional","affiliation":[{"name":"Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Vaeth","sequence":"additional","affiliation":[{"name":"Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA"},{"name":"Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7197-912X","authenticated-orcid":false,"given":"Rahul N.","family":"Kanadia","sequence":"additional","affiliation":[{"name":"Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA"},{"name":"Institute for System Genomics, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042701001401000_DEV190967C1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1747-1028-1-18","article-title":"Cdc45-MCM-GINS, a new power player for DNA replication","volume":"1","author":"Aparicio","year":"2006","journal-title":"Cell Div."},{"key":"2021042701001401000_DEV190967C2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/emmm.201303573","article-title":"Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency","volume":"6","author":"Argente","year":"2014","journal-title":"EMBO Mol. 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