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Complex alternative splicing partially inactivates the human chorionic somatomammotropin-like (hCS-L) gene
A Misra-Press1, N E Cooke, S A Liebhaber
1Howard Hughes Medical Institute, Philadelphia, Pennsylvania.
The Journal of Biological Chemistry
|September 16, 1994
Summary
The human chorionic somatomammotropin-L (hCS-L) gene is expressed in the placenta, contrary to previous assumptions. Analysis reveals complex alternative splicing, with most transcripts being nonfunctional, but some may encode novel gestational hormones.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- The human growth hormone/human chorionic somatomammotropin (hGH/hCS) gene cluster includes five genes, with hCS-L previously considered a pseudogene.
- hCS-L expression in the placenta has been detected, but its transcript processing is obscured by similar hCS-A and hCS-B transcripts.
Purpose of the Study:
- To investigate the alternative splicing pathways and mRNA structure of the hCS-L gene.
- To determine the functional potential of hCS-L transcripts in placental expression.
Main Methods:
- Establishment of stably transfected cell lines for selective hCS-L gene expression.
- Analysis of hCS-L mRNA splicing patterns using transfected cell lines and placental RNA.
- In vitro translation of specific hCS-L mRNA isoforms.
Main Results:
- At least five alternative splicing pathways for hCS-L mRNA were identified.
- High frequency of exon 2 skipping (73%) and alternative exon 3 splice acceptor site utilization were observed.
- Three low-abundance hCS-L mRNAs with extended open reading frames were identified, with two containing exon 2.
Conclusions:
- The hCS-L gene is expressed in the human placenta with complex alternative splicing.
- The majority of processed hCS-L mRNAs are predicted to be nonfunctional due to splicing patterns.
- Specific low-abundance hCS-L transcripts may encode novel gestational hormones.