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Alternatively spliced exons encode the tissue-specific 5' termini of leukocyte pp52 and stromal cell S37 mRNA
A A Thompson1, S A Omori, M J Gilly
1Department of Pediatrics, UCLA School of Medicine 90095, USA.
Abstract:
The pp52 gene encodes an intracellular, F-actin-binding phosphoprotein (also designated LSP1 and WP34) postulated to function in cytoskeleton dynamics and cell motility. We previously reported that different mRNA isoforms are expressed from this gene in cells of the leukocyte lineage versus mesodermally derived cells. These tissue-specific mRNA isoforms are identical except for 5'-untranslated regions and sequences coding for unique N-termini of 23 and 21 amino acids, respectively. As this is a single-copy gene, we predicted that these tissue-specific mRNA isoforms would be generated by alternative RNA splicing. We report that the unique 5' sequences in these mRNA isoforms are encoded in two separate exons containing ATG initiation codons. These features confirm that the pp52 and S37 mRNA isoforms are generated by alternative RNA splicing and establish that they are independently translated. Other results presented here indicate that the differential expression of these exons in leukocytes versus mesodermally derived cells is regulated at the level of transcription by tissue-specific promoters.
Insights
The pp52 gene generates distinct mRNA isoforms in different cell types through alternative RNA splicing. Tissue-specific promoters regulate the transcription of these unique exons, impacting cytoskeleton dynamics and cell motility.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The pp52 gene encodes a phosphoprotein involved in cytoskeleton dynamics and cell motility.
- Previous studies indicated tissue-specific mRNA isoforms of pp52 in leukocyte and mesodermally derived cells.
- These isoforms differ in 5'-untranslated regions and unique N-terminal sequences.
Purpose of the Study:
- To investigate the mechanism generating tissue-specific mRNA isoforms of the pp52 gene.
- To confirm the role of alternative RNA splicing in pp52 expression.
- To elucidate the regulatory mechanisms controlling differential gene expression.
Main Methods:
- Analysis of mRNA sequences and gene structure.
- Identification and characterization of unique exons.
- Investigation of transcriptional regulation using tissue-specific promoters.
Main Results:
- The unique 5' sequences of pp52 mRNA isoforms are encoded in two separate exons, each containing an ATG initiation codon.
- Alternative RNA splicing generates the distinct pp52 (also known as LSP1 and WP34) and S37 mRNA isoforms.
- Differential expression of these exons is controlled by tissue-specific promoters at the transcriptional level.
Conclusions:
- Alternative RNA splicing and independent translation generate distinct pp52 mRNA isoforms.
- Tissue-specific promoters regulate the transcription of unique exons, controlling differential gene expression.
- These findings provide insight into the regulation of cytoskeleton dynamics and cell motility.