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The Methyl CpG Binding Protein 2 (Mecp2) gene, whose mutations cause Rett syndrome, generates two protein isoforms, MeCP2E1 and MeCP2E2, by alternative splicing. These isoforms likely possess non-redundant functions. However, the molecular mechanism for Mecp2 pre-mRNA alternative splicing remains to be understood. Here, we analyzed the alternative splicing mechanism of MeCP2 pre-mRNA and found that exon 2 is efficiently recognized through adjacent strong splice sites. In addition, exonic splicing enhancer (ESE) in exon 2 plays an important role in exon 2 inclusion, which is highly likely to be mediated by SRSF9.<\/jats:p>","DOI":"10.3390\/ijms26073319","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T16:19:16Z","timestamp":1743610756000},"page":"3319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SRSF9-Mediated Exon Recognition Promotes Exon 2 Inclusion in Mecp2 Pre-mRNA Alternative Splicing"],"prefix":"10.3390","volume":"26","author":[{"given":"Saya","family":"Oshizuki","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Masaki","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-550X","authenticated-orcid":false,"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-7420","authenticated-orcid":false,"given":"Naoyuki","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cell.2009.02.009","article-title":"The spliceosome: Design principles of a dynamic RNP machine","volume":"136","author":"Wahl","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrg3778","article-title":"Context-dependent control of alternative splicing by RNA-binding proteins","volume":"15","author":"Fu","year":"2014","journal-title":"Nat. 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