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...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2024-03-01
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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. |
first_indexed | 2024-03-07T21:53:27Z |
format | Article |
id | doaj.art-94fa1dcaea7b4dec946a0cdfaa05847d |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-03-07T21:53:27Z |
publishDate | 2024-03-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
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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