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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Several mRNAs with variable 3' untranslated regions and different stability encode the human PR264/SC35 splicing
Abstract:
We have recently established that several mRNAs encode the PR264/SC35 splicing factor and that their expression is related to that of c-Myb in human hematopoietic cells. We now report that the various PR264 mRNAs whose expression is transactivated by c-Myb proteins encode an identical PR264/SC35 polypeptide. These mRNAs differ only in their 3' untranslated sequences and exhibit significantly different half-lives. We also show that there is a direct correlation between the length of the 3' untranslated region and the stability of the mRNA species. Given that 5' and 3' splice site selection mediated by the PR264/SC35 splicing factor is concentration-dependent, we postulate that alternative splicing of the 3' untranslated sequences might represent another key element in regulating the levels of PR264/SC35 expression during hematopoietic differentiation.
Insights
The PR264/SC35 splicing factor is regulated by c-Myb in hematopoietic cells. Alternative splicing of 3' untranslated regions affects PR264/SC35 mRNA stability and expression levels.
Area of Science:
- Molecular Biology
- Gene Regulation
- Hematopoiesis
Background:
- The PR264/SC35 splicing factor plays a crucial role in RNA splicing.
- PR264/SC35 expression is linked to c-Myb in human hematopoietic cells.
Purpose of the Study:
- To investigate the relationship between c-Myb and PR264/SC35 mRNA variants.
- To determine how alternative 3' untranslated regions influence PR264/SC35 mRNA stability and expression.
Main Methods:
- Analysis of PR264 mRNA variants and their 3' untranslated sequences.
- Assessment of mRNA half-lives and correlation with 3' UTR length.
- Investigation of c-Myb transactivation of PR264 mRNA expression.
Main Results:
- Multiple PR264 mRNAs, transactivated by c-Myb, encode an identical PR264/SC35 polypeptide.
- These mRNAs differ in their 3' untranslated regions (UTRs) and exhibit distinct half-lives.
- A direct correlation exists between 3' UTR length and mRNA stability.
Conclusions:
- Alternative splicing of 3' UTRs in PR264 mRNAs contributes to regulating PR264/SC35 protein levels.
- This mechanism may be critical for controlling PR264/SC35 expression during hematopoietic differentiation.
- PR264/SC35 concentration-dependent splicing activity suggests a feedback loop involving 3' UTRs.
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