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Novel RNA-Binding Proteins Isolation by the RaPID Methodology
Published on: September 30, 2016
SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and
Seung Kuk Park1, Sunjoo Jeong1
1Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do, Republic of Korea.
Abstract:
Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.
Insights
The splicing factor SRSF3 regulates tumor suppressor PDCD4 expression. SRSF3 affects PDCD4 mRNA splicing and export, and translation, coordinating protein levels in cancer cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Gene expression involves multiple regulatory steps.
- SR proteins, including SRSF3, play diverse roles.
- SRSF3 is a tumor-related splicing factor.
Purpose of the Study:
- To determine if SRSF3 regulates tumor-suppressor PDCD4 expression at multiple steps.
- To investigate the mechanisms by which SRSF3 influences PDCD4 isoforms.
Main Methods:
- Knockdown of SRSF3 in SW480 colon cancer cells.
- Analysis of alternative splicing, nuclear export, and translation of PDCD4 mRNA isoforms.
- Western blot analysis to assess PDCD4 protein levels.
Main Results:
- Knockdown of SRSF3 increased PDCD4 protein levels.
- SRSF3 repressed alternative splicing and nuclear export of minor PDCD4 mRNA isoforms.
- SRSF3 repressed translation of the major PDCD4 mRNA isoform.
- Translation of minor PDCD4 mRNA isoforms was unaffected by SRSF3.
Conclusions:
- SRSF3 coordinates PDCD4 protein expression through distinct mechanisms on alternatively spliced mRNA isoforms.
- Overexpression of SRSF3 may contribute to reduced PDCD4 protein levels in various cancer types.
- SRSF3 acts as a key regulator in the expression of the tumor suppressor PDCD4.
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