{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T01:54:23Z","timestamp":1775872463035,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The c.620\u00a0T\u2009&amp;gt;\u2009G mutation in rhodopsin found in the first mapped autosomal dominant retinitis pigmentosa (adRP) locus is associated with severe, early-onset RP. Intriguingly, another mutation affecting the same nucleotide (c.620\u00a0T\u2009&amp;gt;\u2009A) is related to a mild, late-onset RP. Assuming that both mutations are missense mutations (Met207Arg and Met207Lys) hampering the ligand-binding pocket, previous work addressed how they might differentially impair rhodopsin function. Here, we investigated the impact of both mutations at the mRNA and protein level in HEK293 cells and in the mouse retina. We show that, in contrast to c.620\u00a0T\u2009&amp;gt;\u2009A, c.620\u00a0T\u2009&amp;gt;\u2009G is a splicing mutation, which generates an exceptionally strong splice acceptor site (SAS) resulting in a 90\u00a0bp in-frame deletion and protein mislocalization in vitro and in vivo. Moreover, we identified the core element underlying the c.620\u00a0T\u2009&amp;gt;\u2009G SAS strength. Finally, we demonstrate that the c.620\u00a0T\u2009&amp;gt;\u2009G SAS is very flexible in branch point choice, which might explain its remarkable performance. Based on these results, we suggest that (i) point mutations should be routinely tested for mRNA splicing to avoid dispensable analysis of mutations on protein level, which do not naturally exist. (ii) Puzzling disease courses of mutations in other genes might also correlate with their effects on mRNA splicing. (iii) Flexibility in branch point choice might be another factor influencing the SAS strength. (iv) The core splice element identified in this study could be useful for biotechnological applications requiring effective SAS.<\/jats:p>","DOI":"10.1093\/hmg\/ddz291","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T20:14:26Z","timestamp":1575490466000},"page":"295-304","source":"Crossref","is-referenced-by-count":10,"title":["Enigmatic rhodopsin mutation creates an exceptionally strong splice acceptor site"],"prefix":"10.1093","volume":"29","author":[{"given":"Lisa M","family":"Riedmayr","sequence":"first","affiliation":[{"name":"Center for Integrated Protein Science Munich (CIPSM), 81377 Munich, Germany"},{"name":"Department of Pharmacy\u2014Center for Drug Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sybille","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science Munich (CIPSM), 81377 Munich, Germany"},{"name":"Department of Pharmacy\u2014Center for Drug Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Biel","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science Munich (CIPSM), 81377 Munich, Germany"},{"name":"Department of Pharmacy\u2014Center for Drug Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvir","family":"Becirovic","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science Munich (CIPSM), 81377 Munich, Germany"},{"name":"Department of Pharmacy\u2014Center for Drug Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2020020604331250900_ref1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s13353-018-0444-7","article-title":"Splicing mutations in human genetic disorders: examples, detection, and confirmation","volume":"59","author":"Anna","year":"2018","journal-title":"J. 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