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SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs
A Sureau1, R Gattoni, Y Dooghe
1CNRS-UMR 146, Institut Curie, Bât. 110, Centre Universitaire, 91405 Orsay, France.
The EMBO Journal
|April 4, 2001
Summary
SR proteins like SC35 regulate gene expression. This study shows SC35 controls its own mRNA levels by activating splicing events that produce unstable mRNA, a novel self-regulatory mechanism.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Processing
Background:
- SC35 is an SR protein involved in alternative splicing.
- SC35 expression is regulated by alternatively spliced mRNAs with varying stabilities.
Purpose of the Study:
- To investigate the autoregulatory mechanisms of SC35.
- To determine how SC35 overexpression affects its own mRNA levels and splicing.
Main Methods:
- Overexpression of SC35 in HeLa cells.
- Analysis of endogenous SC35 mRNA levels and alternative splicing.
- In vitro splicing assays with recombinant SR proteins.
Main Results:
- SC35 overexpression decreased endogenous SC35 mRNA levels.
- SC35 specifically activated alternative splicing events in its own 3' UTR, leading to exon inclusion and intron excision.
- The resulting alternatively spliced mRNA was highly unstable, likely due to mRNA surveillance.
Conclusions:
- SC35 autoregulates its expression through alternative splicing.
- This process generates an unstable mRNA, representing a novel feedback loop.
- SC35 is the first identified splicing factor to control its own expression via unstable mRNA production.