Alternative mRNA splicing events and regulators in epidermal differentiation

Summary: 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 invol...

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Main Authors: Shota Takashima, Wujianan Sun, Auke B.C. Otten, Pengfei Cai, Shaohong Isaac Peng, Elton Tong, Jolina Bui, McKenzie Mai, Oyumergen Amarbayar, Binbin Cheng, Rowen Jane Odango, Zongkai Li, Kun Qu, Bryan K. Sun
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724001426
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author Shota Takashima
Wujianan Sun
Auke B.C. Otten
Pengfei Cai
Shaohong Isaac Peng
Elton Tong
Jolina Bui
McKenzie Mai
Oyumergen Amarbayar
Binbin Cheng
Rowen Jane Odango
Zongkai Li
Kun Qu
Bryan K. Sun
author_facet Shota Takashima
Wujianan Sun
Auke B.C. Otten
Pengfei Cai
Shaohong Isaac Peng
Elton Tong
Jolina Bui
McKenzie Mai
Oyumergen Amarbayar
Binbin Cheng
Rowen Jane Odango
Zongkai Li
Kun Qu
Bryan K. Sun
author_sort Shota Takashima
collection DOAJ
description Summary: 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.
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spelling doaj.art-94fa1dcaea7b4dec946a0cdfaa05847d2024-02-25T04:35:36ZengElsevierCell Reports2211-12472024-03-01433113814Alternative mRNA splicing events and regulators in epidermal differentiationShota Takashima0Wujianan Sun1Auke B.C. Otten2Pengfei Cai3Shaohong Isaac Peng4Elton Tong5Jolina Bui6McKenzie Mai7Oyumergen Amarbayar8Binbin Cheng9Rowen Jane Odango10Zongkai Li11Kun Qu12Bryan K. Sun13Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, ChinaDepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, ChinaDepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USADepartment of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, ChinaDepartment of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, ChinaDepartment of Dermatology, University of California San Diego, La Jolla, CA 92109, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724001426CP: Stem cell researchCP: Molecular biology
spellingShingle Shota Takashima
Wujianan Sun
Auke B.C. Otten
Pengfei Cai
Shaohong Isaac Peng
Elton Tong
Jolina Bui
McKenzie Mai
Oyumergen Amarbayar
Binbin Cheng
Rowen Jane Odango
Zongkai Li
Kun Qu
Bryan K. Sun
Alternative mRNA splicing events and regulators in epidermal differentiation
Cell Reports
CP: Stem cell research
CP: Molecular biology
title Alternative mRNA splicing events and regulators in epidermal differentiation
title_full Alternative mRNA splicing events and regulators in epidermal differentiation
title_fullStr Alternative mRNA splicing events and regulators in epidermal differentiation
title_full_unstemmed Alternative mRNA splicing events and regulators in epidermal differentiation
title_short Alternative mRNA splicing events and regulators in epidermal differentiation
title_sort alternative mrna splicing events and regulators in epidermal differentiation
topic CP: Stem cell research
CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124724001426
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