biostudies-literatureTakashima SNIAMSNHGRI NIH HHSNational Institutes of HealthNIAMS NIH HHSNational Human Genome Research Institute113814https://www.ebi.ac.uk/biostudies/studies/S-EPMC11293371biostudies-literatureUnknown43(3)Alternative splicing (AS) of messenger RNAs occurs in ∼95% of multi-exon human genes and generates diverse RNA and protein isoforms. We investigated AS events associated with human epidermal differentiation, a process crucial for skin function. We identified 6,413 AS events, primarily involving cassette exons. We also predicted 34 RNA-binding proteins (RBPs) regulating epidermal AS, including 19 previously undescribed candidate regulators. From these results, we identified FUS as an RBP that regulates the balance between keratinocyte proliferation and differentiation. Additionally, we characterized the function of a cassette exon AS event in MAP3K7, which encodes a kinase involved in cell signaling. We found that a switch from the short to long isoform of MAP3K7, triggered during differentCell reportsAlternative mRNA splicing events and regulators in epidermal differentiation.PMC11293371K08 AR067853DP2 HG012441DP2HG012441K08AR067853Peng SICai PCheng BMai MQu KOtten ABCSun WOdango RJTakashima SLi ZAmarbayar OBui JSun BKTong EfalseAlternative mRNA splicing events and regulators in epidermal differentiation.Alternative splicing (AS) of messenger RNAs occurs in ∼95% of multi-exon human genes and generates diverse RNA and protein isoforms. We investigated AS events associated with human epidermal differentiation, a process crucial for skin function. We identified 6,413 AS events, primarily involving cassette exons. We also predicted 34 RNA-binding proteins (RBPs) regulating epidermal AS, including 19 previously undescribed candidate regulators. From these results, we identified FUS as an RBP that regulates the balance between keratinocyte proliferation and differentiation. Additionally, we characterized the function of a cassette exon AS event in MAP3K7, which encodes a kinase involved in cell signaling. We found that a switch from the short to long isoform of MAP3K7, triggered during different2024-01-01T00:00:00Z2024 Mar2026-06-03T00:56:56.829Z2025-04-19T20:48:08.325ZS-EPMC112933713840258510.1016/j.celrep.2024.113814