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Identification of factors affecting the activity of these enzymes could help modulate mutagenesis and associated clinical outcomes. Here, we show that canonical and alternatively spliced\n                    <jats:italic>A3A<\/jats:italic>\n                    and\n                    <jats:italic>A3B<\/jats:italic>\n                    isoforms produce corresponding mutagenic and non-mutagenic enzymes. Increased expression of the mutagenic\n                    <jats:italic>A3B<\/jats:italic>\n                    isoform predicted shorter progression-free survival in bladder cancer. We demonstrate that the production of mutagenic vs. non-mutagenic A3B protein isoforms was considerably affected by inclusion\/skipping of exon 5 in\n                    <jats:italic>A3B<\/jats:italic>\n                    . Furthermore, exon 5 skipping, resulting in lower levels of mutagenic A3B enzyme, could be increased in vitro. Specifically, we showed the effects of treatment with an SF3B1 inhibitor affecting spliceosome interaction with a branch point site in intron 4, or with splice-switching oligonucleotides targeting exon 5 of\n                    <jats:italic>A3B<\/jats:italic>\n                    . Our results underscore the clinical role of A3B and implicate alternative splicing of\n                    <jats:italic>A3B<\/jats:italic>\n                    as a mechanism that could be targeted to restrict APOBEC-mediated mutagenesis.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-01844-5","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T07:03:43Z","timestamp":1616396623000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting natural splicing plasticity of APOBEC3B restricts its expression and mutagenic activity"],"prefix":"10.1038","volume":"4","author":[{"given":"A.","family":"Rouf Banday","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-2380","authenticated-orcid":false,"given":"Olusegun O.","family":"Onabajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seraph Han-Yin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeola","family":"Obajemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0925","authenticated-orcid":false,"given":"Joselin M.","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3370-8542","authenticated-orcid":false,"given":"Krista A.","family":"Delviks-Frankenberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-7724","authenticated-orcid":false,"given":"Philippe","family":"Lamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariunaa","family":"Bayanjargal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Zettelmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-2612","authenticated-orcid":false,"given":"Oscar","family":"Florez-Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-8412","authenticated-orcid":false,"given":"Vinay K.","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7061-9851","authenticated-orcid":false,"given":"Lars","family":"Dyrskj\u00f8t","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-2091","authenticated-orcid":false,"given":"Ludmila","family":"Prokunina-Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"1844_CR1","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1038\/ng.3670","volume":"48","author":"CD Middlebrooks","year":"2016","unstructured":"Middlebrooks, C. 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