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Updated: Aug 9, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins
Abstract:
The MUC4 mucin gene encodes a putative membrane-anchored mucin with predicted size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850-kDa mucin-type subunit MUC4alpha and the 80-kDa membrane-associated subunit MUC4beta. In this study, we cloned and characterized unique MUC4 cDNA sequences that differ from the originally published sequence. Eight alternative splice events located downstream of the central large tandem repeat array generated eight new, distinct cDNAs. The deduced sequences of these MUC4 cDNAs (sv1-MUC4 to sv8-MUC4, the full length cDNA being called sv0-MUC4) provided seven distinct variants, five secreted forms and two membrane-associated forms. Furthermore, two other alternative splicing events located on both sides of the tandem repeat array created two variants, MUC4/Y and MUC4/X, both lacking the central tandem repeat. Therefore, MUC4 can be expressed in three distinct forms, one membrane-bound, one secreted, and one lacking the hallmark feature of mucin, the tandem repeat array. Although no specific function has yet been discovered for the family of proteins putatively produced from the unique MUC4 gene, we suspect that the MUC4 proteins may be implicated in the integrity and renewal of the epithelium.
Insights
The MUC4 mucin gene produces diverse protein variants through alternative splicing. These forms include secreted, membrane-bound, and tandem repeat-lacking mucins, potentially impacting epithelial integrity.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The MUC4 mucin gene encodes a large, membrane-anchored mucin composed of MUC4alpha and MUC4beta subunits.
- Previous studies established the basic structure of the MUC4 gene and its protein product.
Purpose of the Study:
- To identify and characterize novel MUC4 cDNA sequences generated by alternative splicing.
- To determine the structural diversity of MUC4 protein isoforms.
Main Methods:
- Cloning of unique MUC4 cDNA sequences.
- Analysis of alternative splicing events within the MUC4 gene.
- Deduction of protein sequences from novel cDNA variants.
Main Results:
- Eight alternative splice events downstream of the tandem repeat array yielded seven new MUC4 variants (sv1-MUC4 to sv8-MUC4).
- These variants included five secreted and two membrane-associated forms.
- Two additional splicing events flanking the tandem repeat array generated MUC4/Y and MUC4/X, lacking the central tandem repeat.
Conclusions:
- The MUC4 gene exhibits extensive alternative splicing, producing at least three distinct protein forms: membrane-bound, secreted, and tandem repeat-lacking.
- These diverse MUC4 protein variants may play a role in maintaining epithelial integrity and renewal.
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