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We previously showed that premature polyadenylation (pPA) of <jats:italic>MAGI3<\/jats:italic> truncates the gene, switching its functional role from a TSG to a dominant-negative oncogene. Here we report that <jats:italic>MAGI3<\/jats:italic> undergoes pPA at the intron immediately downstream of its large internal exon, which is normally highly modified by N<jats:sup>6<\/jats:sup>-methyladenosine (m<jats:sup>6<\/jats:sup>A). In breast cancer cells that upregulate <jats:italic>MAGI3<\/jats:italic><jats:sup>\n                  <jats:italic>pPA<\/jats:italic>\n                <\/jats:sup>, m<jats:sup>6<\/jats:sup>A levels in the large internal exon of <jats:italic>MAGI3<\/jats:italic> are significantly reduced compared to cells that do not express <jats:italic>MAGI3<\/jats:italic><jats:sup>\n                  <jats:italic>pPA<\/jats:italic>\n                <\/jats:sup>. We further find that <jats:italic>MAGI3<\/jats:italic><jats:sup>\n                  <jats:italic>pPA<\/jats:italic>\n                <\/jats:sup> transcripts are significantly depleted of m<jats:sup>6<\/jats:sup>A modifications, in contrast to highly m<jats:sup>6<\/jats:sup>A-modified full-length <jats:italic>MAGI3<\/jats:italic> mRNA. Finally, we analyze public expression data and find that other TSGs, including <jats:italic>LATS1<\/jats:italic> and <jats:italic>BRCA1<\/jats:italic>, also undergo intronic pPA following large internal exons, and that m<jats:sup>6<\/jats:sup>A levels in these exons are reduced in pPA-activated breast cancer cells relative to untransformed mammary cells. Our study suggests that m<jats:sup>6<\/jats:sup>A may play a role in regulating intronic pPA of <jats:italic>MAGI3<\/jats:italic> and possibly other TSGs, warranting further investigation.<\/jats:p>","DOI":"10.1038\/s41598-018-19916-8","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T11:13:37Z","timestamp":1516187617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Premature polyadenylation of MAGI3 is associated with diminished N6-methyladenosine in its large internal exon"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-0593","authenticated-orcid":false,"given":"Thomas K.","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica S.","family":"Elman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexter X.","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush B.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Kuperwasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,23]]},"reference":[{"key":"19916_CR1","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1101\/gad.17268411","volume":"25","author":"NJ Proudfoot","year":"2011","unstructured":"Proudfoot, N. 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