Pas1c1 is a candidate for the mouse pulmonary adenoma susceptibility 1 locus
Min Wang1, Manabu Futamura, Yian Wang
1Department of Surgery and The Alvin J Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA.
Abstract:
Pas1 candidate 1 (Pas1c1) gene (also named Lmna-rs1) was found to encode two alternatively spliced mRNA transcripts (i.e. Pas1c1-Va and Pas1c1-Vb). In this study, we identified three additional mRNA transcripts encoded by the Pas1c1 gene, which were designated as Pas1c1-Vc, Pas1c1-Vd, and Pas1c1-Ve, respectively. Similar to Pas1c1-Vb, the newly identified transcripts were only expressed in mouse lung tissues from strains carrying the Pas1-susceptible (Pas1/s) allele. Pas1c1 transcripts were also detected in heart, testis, or brain but not in liver, spleen, or kidney. An 11-nucleotide polymorphism was found within the 3'-acceptor splice site of exon 8, which cosegregates with mouse strain Pas1 alleles and may underlie the strain-specific exon 8 skipping. We also found that ectopic expression of the Pas1c1-Va and Pas1c1-Vb in COS7 and NIH3T3 cells exhibited distinct intracellular distributions. These results support that Pas1c1 as a candidate for the Pas1 locus and the strain-specific isoforms may have differential effects on cell proliferation.
Insights
The Pas1 candidate 1 (Pas1c1) gene produces five mRNA transcripts, with three newly identified isoforms exclusively found in susceptible mouse lung tissues. Strain-specific alternative splicing of Pas1c1 may influence cell proliferation.
Area of Science:
- Genetics
- Molecular Biology
- Gene Expression
Background:
- The Pas1 candidate 1 (Pas1c1) gene, also known as Lmna-rs1, was previously reported to encode two alternatively spliced mRNA transcripts (Pas1c1-Va and Pas1c1-Vb).
- Understanding the full spectrum of Pas1c1 gene products and their tissue-specific expression is crucial for investigating its role in the Pas1 locus.
Purpose of the Study:
- To identify and characterize novel mRNA transcripts encoded by the Pas1c1 gene.
- To investigate the tissue distribution and strain-specific expression patterns of Pas1c1 transcripts.
- To explore the potential mechanism underlying strain-specific alternative splicing and its functional implications.
Main Methods:
- Identification of novel mRNA transcripts using molecular cloning and sequencing techniques.
- Analysis of tissue distribution of Pas1c1 transcripts in different mouse strains via RT-PCR.
- Investigation of genetic variations, specifically polymorphisms in splice sites, associated with strain-specific splicing.
- Ectopic expression studies in cell lines (COS7 and NIH3T3) to assess intracellular localization of different isoforms.
Main Results:
- Three new mRNA transcripts (Pas1c1-Vc, Pas1c1-Vd, and Pas1c1-Ve) were identified, in addition to the previously known Pas1c1-Va and Pas1c1-Vb.
- The newly identified transcripts, similar to Pas1c1-Vb, were predominantly expressed in lung tissues of mice carrying the Pas1-susceptible (Pas1/s) allele.
- Pas1c1 transcripts were detected in heart, testis, and brain, but absent in liver, spleen, and kidney.
- An 11-nucleotide polymorphism within the 3'-acceptor splice site of exon 8 was identified, correlating with mouse strain Pas1 alleles and potentially causing strain-specific exon 8 skipping.
- Ectopic expression of Pas1c1-Va and Pas1c1-Vb in cultured cells revealed distinct intracellular distributions.
Conclusions:
- The Pas1c1 gene encodes at least five alternatively spliced mRNA transcripts.
- The strain-specific expression of certain Pas1c1 isoforms, particularly in lung tissue, suggests a role in the genetic susceptibility associated with the Pas1 locus.
- The identified polymorphism in the exon 8 splice site offers a plausible explanation for the observed strain-specific alternative splicing.
- Differential intracellular localization of Pas1c1 isoforms may indicate distinct functional roles, potentially impacting cell proliferation.
