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Here we report exon 6B, a novel exon, generated by exonization of an intronic Alu-like sequence of <jats:italic>SMN<\/jats:italic>. We validate the expression of exon 6B-containing transcripts <jats:italic>SMN6B<\/jats:italic> and <jats:italic>SMN6B\u03947<\/jats:italic> in human tissues and cell lines. We confirm generation of <jats:italic>SMN6B<\/jats:italic> transcripts from both <jats:italic>SMN1<\/jats:italic> and <jats:italic>SMN2<\/jats:italic>. We detect expression of SMN6B protein using antibodies raised against a unique polypeptide encoded by exon 6B. We analyze RNA-Seq data to show that hnRNP C is a potential regulator of <jats:italic>SMN6B<\/jats:italic> expression and demonstrate that <jats:italic>SMN6B<\/jats:italic> is a substrate of nonsense-mediated decay. We show interaction of SMN6B with Gemin2, a critical SMN-interacting protein. We demonstrate that SMN6B is more stable than SMN\u03947 and localizes to both the nucleus and the cytoplasm. Our finding expands the diversity of transcripts generated from human <jats:italic>SMN<\/jats:italic> genes and reveals a novel protein isoform predicted to be stably expressed during conditions of stress.<\/jats:p>","DOI":"10.1038\/srep30778","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T09:28:32Z","timestamp":1470130112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein"],"prefix":"10.1038","volume":"6","author":[{"given":"Joonbae","family":"Seo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia N.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Ottesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra N.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,2]]},"reference":[{"key":"BFsrep30778_CR1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nature08909","volume":"463","author":"TW Nilsen","year":"2010","unstructured":"Nilsen, T. 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