{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:51:18Z","timestamp":1768427478149,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wires.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The neurofibromatosis type 1 (<jats:italic>NF1<\/jats:italic>) gene has 61 exons. The major alternative exon in <jats:italic>NF1<\/jats:italic> pre\u2010mRNA is exon 23a. Skipping and inclusion of this exon produce isoform I and isoform II neurofibromin, respectively. When the alternative exon was discovered in 1993, several experiments conducted in yeast and human cell lines quickly led to the conclusion that inclusion of this exon reduced the RasGAP function of the neurofibromin protein by 5\u201310\u2010fold. Since then, research efforts on this seemingly important alternative splicing event have been sporadic, leaving many important questions unanswered, until after 2020 when several important papers related to the structure and function of exon 23a have been published. Two major advancements have been made. First, the cryo\u2010EM structures of the full\u2010length neurofibromin, of both isoforms, have been solved. More excitingly, the structure of isoform II neurofibromin that includes exon 23a provides important insight into why this isoform has reduced RasGAP activity. Second, the role of the altered splicing pattern of exon 23a in the development of high\u2010grade glioma (HGG) has been investigated. In this review, we start with the introduction of alternative splicing of exon 23a, its discovery, differential expression patterns, and regulatory mechanisms that control this alternative splicing event. Next, we discuss the structural differences between the two isoforms which give insight into the differing RasGAP activities. We then review the in\u00a0vivo biological function of the regulated inclusion of exon 23a, focusing on cognitive behaviors and brain tumor development. Finally, we briefly discuss the future directions of studies on NF1 exon 23a.<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>RNA Processing &gt; Splicing Regulation\/Alternative Splicing<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.70021","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:15:07Z","timestamp":1755216907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alternative Splicing of Exon 23a in Neurofibromatosis Type 1 Pre\u2010<scp>mRNA<\/scp>: Its Contribution to the Protein Structure and Function of Neurofibromin"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-3127","authenticated-orcid":false,"given":"Annabelle G.","family":"Elsner Pacheco","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences 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