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Apoptosis is a pathway that helps maintain cell population homeostasis in tissues. Evasion and resistance to apoptosis are major hallmarks of cancer cells while its activation is often responsible for the cytotoxicity of chemotherapeutic drugs. Disruption of the apoptotic pathway or overexpression of anti-apoptotic proteins significantly contributes to the resistance of cancer cells to anti-cancer treatments.
More than 200 pro- and anti-apoptotic proteins control the apoptotic process. Most of the genes encoding proteins involved in apoptosis are alternatively spliced and proteins of opposing functions are often produced from a common pre-mRNA. Thus, alternative splicing plays a crucial role in the regulation of apoptosis. Numerous factors control alternative splicing as part of combinatorial strategies. However, although hnRNP proteins are powerful modulators of splice site selection, their general role in the splicing control of apoptotic genes is poorly documented.
The RNA Binding Protein(RBP) Group undertook a large-scale systematic analysis of the role of hnRNP proteins in the control of alternative splicing of a subset of apoptotic genes. The study is based on loss-of-function approach using siRNA technology and high-throughput monitoring of splicing events by RT-PCR, providing a first glimpse into the complex influence of hnRNP proteins on alternative splicing of apoptotic genes, and offering an outline of the hnRNP protein networks that regulate these alternative splicing events.