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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Oncogenic splicing factor SRSF3 regulates ILF3 alternative splicing to promote cancer cell proliferation and
Rong Jia1,2, Masahiko Ajiro1, Lulu Yu1
1Tumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.
Abstract:
Alternative RNA splicing is an important focus in molecular and clinical oncology. We report here that SRSF3 regulates alternative RNA splicing of interleukin enhancer binding factor 3 (ILF3) and production of this double-strand RNA-binding protein. An increased coexpression of ILF3 isoforms and SRSF3 was found in various types of cancers. ILF3 isoform-1 and isoform-2 promote cell proliferation and transformation. Tumor cells with reduced SRSF3 expression produce aberrant isoform-5 and -7 of ILF3. By binding to RNA sequence motifs, SRSF3 regulates the production of various ILF3 isoforms by exclusion/inclusion of ILF3 exon 18 or by selection of an alternative 3' splice site within exon 18. ILF3 isoform-5 and isoform-7 suppress tumor cell proliferation and the isoform-7 induces cell apoptosis. Our data indicate that ILF3 isoform-1 and isoform-2 are two critical factors for cell proliferation and transformation. The increased SRSF3 expression in cancer cells plays an important role in maintaining the steady status of ILF3 isoform-1 and isoform-2.
Insights
SRSF3 protein controls alternative splicing of interleukin enhancer binding factor 3 (ILF3) in cancer. Aberrant ILF3 forms can suppress or promote tumor growth, impacting cell proliferation and apoptosis.
Area of Science:
- Molecular Oncology
- RNA Biology
- Cancer Research
Background:
- Alternative RNA splicing is crucial in cancer development.
- Interleukin enhancer binding factor 3 (ILF3) is a double-strand RNA-binding protein involved in cellular processes.
Purpose of the Study:
- To investigate the role of SRSF3 in regulating alternative splicing of ILF3.
- To understand how ILF3 isoforms affect cancer cell proliferation and transformation.
Main Methods:
- Analysis of SRSF3 and ILF3 coexpression in various cancer types.
- Investigating the mechanism of SRSF3-mediated ILF3 alternative splicing.
- Assessing the impact of different ILF3 isoforms on tumor cell behavior.
Main Results:
- SRSF3 regulates ILF3 alternative splicing, affecting exon 18 inclusion/exclusion and 3' splice site selection.
- Increased SRSF3 expression in cancer maintains ILF3 isoforms that promote proliferation.
- Aberrant ILF3 isoforms (isoform-5 and -7) produced upon reduced SRSF3 expression suppress proliferation and induce apoptosis.
Conclusions:
- SRSF3 plays a critical role in maintaining oncogenic ILF3 isoforms in cancer cells.
- ILF3 isoforms exhibit dual roles in cancer, with some promoting proliferation and others suppressing it.
- Targeting SRSF3-mediated ILF3 splicing represents a potential therapeutic strategy in oncology.
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