Cryptic intron activation within the large exon of the mouse polymeric immunoglobulin receptor gene: cryptic splice sites correspond to protein domain boundaries
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Updated: Oct 19, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
S R Bruce1, C S Kaetzel, M L Peterson
1Department of Microbiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Abstract:
The fourth exon of the mouse polymeric immuno-globulin receptor (pIgR) is 654 nt long and, despite being surrounded by large introns, is constitutively spliced into the mRNA. Deletion of an 84 nt sequence from this exon strongly activated both cryptic 5' and 3' splice sites surrounding a 78 nt cryptic intron. The 84 nt deletion is just upstream of the cryptic 3' splice site; the cryptic 3' splice site was likely activated because the deletion created a better 3' splice site. However, the cryptic 5' splice site was also required to activate the cryptic splice reaction; point mutations in either of the cryptic splice sites that decreased their match to the consensus splice site sequence inactivated the cryptic splice reaction. The activation and inactivation of these cryptic splice sites as a pair suggests that they are being co-recognized by the splicing machinery. Interestingly, the large fourth exon of the pIgR gene encodes two immunoglobulin-like extracellular protein domains; the cryptic 3' splice site coincides with the junction between these protein domains. The cryptic 5' splice site is located between protein subdomains where an intron is found in another gene of the immunoglobulin superfamily.
Insights
Deleting a small sequence in the mouse polymeric immuno-globulin receptor (pIgR) gene exon activated cryptic splice sites. This suggests the splicing machinery co-recognizes these sites, influencing gene expression.
Area of Science:
- Molecular Biology
- Genetics
- RNA Splicing
Background:
- The fourth exon of the mouse polymeric immuno-globulin receptor (pIgR) gene is constitutively spliced.
- This exon encodes two immunoglobulin-like extracellular protein domains.
Purpose of the Study:
- To investigate the impact of deleting a specific sequence within the pIgR fourth exon on alternative splicing.
- To determine the role of cryptic splice sites in regulating pIgR gene expression.
Main Methods:
- Deletion mutagenesis of the mouse pIgR fourth exon.
- Analysis of mRNA splicing patterns using sequencing.
- Site-directed mutagenesis of cryptic splice sites.
Main Results:
- Deletion of an 84 nt sequence activated both cryptic 5' and 3' splice sites flanking a 78 nt intron.
- Activation of the cryptic 3' splice site was likely due to creating a better splice site sequence.
- Point mutations inactivating cryptic splice sites abolished the cryptic splicing event, indicating co-recognition.
Conclusions:
- Cryptic splice sites within the pIgR fourth exon can be activated by specific sequence deletions.
- The splicing machinery appears to co-recognize the activated cryptic 5' and 3' splice sites.
- This finding provides insights into the regulation of gene expression and alternative splicing mechanisms.
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