Alternative mRNA splicing events and regulators in epidermal differentiation

• Published in: Cell reports (Cambridge) Vol. 43; no. 3; p. 113814
• Main Authors: Takashima, Shota, Sun, Wujianan, Otten, Auke B.C., Cai, Pengfei, Peng, Shaohong Isaac, Tong, Elton, Bui, Jolina, Mai, McKenzie, Amarbayar, Oyumergen, Cheng, Binbin, Odango, Rowen Jane, Li, Zongkai, Qu, Kun, Sun, Bryan K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2024; Elsevier
• Subjects: alternative splicing; Alternative Splicing - genetics; CP: Molecular biology; CP: Stem cell research; epidermal differentiation; Exons; Humans; MAP3K7; Protein Isoforms - metabolism; RNA Splicing; RNA, Messenger - genetics; RNA, Messenger - metabolism; skin; skin homeostasis; epidermal differentiation; CP: Stem cell research; alternative splicing; skin; CP: Molecular biology; skin homeostasis; MAP3K7
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113814

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 differentiation, enforces the demarcation between proliferating basal progenitors and overlying differentiated strata. Our findings indicate that AS occurs extensively in the human epidermis and has critical roles in skin homeostasis. [Display omitted] •Epidermal differentiation is associated with 6,413 alternative mRNA splicing events•Splicing affects signal transduction, chromatin modification, and other key processes•Alternative splicing of a single exon of MAP3K7 regulates epidermal differentiation Takashima et al. demonstrate that human epidermal differentiation is associated with >6,000 alternative mRNA splicing events. Hundreds of genes undergo alternative splicing without substantial changes to steady-state expression. One such splicing event, involving alternative inclusion of a single exon of MAP3K7, controls the differentiation of epidermal keratinocytes.