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Adama Mickiewicza w Poznaniu","doi-asserted-by":"publisher","award":["05\/IDUB\/2019\/94"],"award-info":[{"award-number":["05\/IDUB\/2019\/94"]}],"id":[{"id":"10.13039\/501100013920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CUG-binding protein, ELAV-like Family Member 1 (CELF1) plays an important role during the development of different tissues, such as striated muscle and brain tissue. CELF1 is an RNA-binding protein that regulates RNA metabolism processes, e.g., alternative splicing, and antagonizes other RNA-binding proteins, such as <jats:italic>Muscleblind<\/jats:italic>-like proteins (MBNLs). Abnormal activity of both classes of proteins plays a crucial role in the pathogenesis of myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults. In this work, we show that alternative splicing of exons forming both the 5\u2032 and 3\u2032 untranslated regions (UTRs) of <jats:italic>CELF1<\/jats:italic> mRNA is efficiently regulated during development and tissue differentiation and is disrupted in skeletal muscles in the context of DM1. Alternative splicing of the <jats:italic>CELF1<\/jats:italic> 5\u2032UTR leads to translation of two potential protein isoforms that differ in the lengths of their N-terminal domains. We also show that the MBNL and CELF proteins regulate the distribution of mRNA splicing isoforms with different 5\u2032UTRs and 3\u2032UTRs and affect the <jats:italic>CELF1<\/jats:italic> expression by changing its sensitivity to specific microRNAs or RNA-binding proteins. Together, our findings show the existence of different mechanisms of regulation of <jats:italic>CELF1<\/jats:italic> expression through the distribution of various 5\u2032 and 3\u2032 UTR isoforms within <jats:italic>CELF1<\/jats:italic> mRNA.<\/jats:p>","DOI":"10.1038\/s41598-021-03901-9","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T11:03:21Z","timestamp":1641553401000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Distribution of alternative untranslated regions within the mRNA of the CELF1 splicing factor affects its expression"],"prefix":"10.1038","volume":"12","author":[{"given":"Arkadiusz","family":"Kajdasz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Niewiadomska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Sekrecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Sobczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"3901_CR1","doi-asserted-by":"publisher","first-page":"4407","DOI":"10.1093\/nar\/24.22.4407","volume":"24","author":"LT Timchenko","year":"1996","unstructured":"Timchenko, L. 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