SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation

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• 作者：Seung Kuk Park ; Sunjoo Jeong ; ^{sjsj@dankook.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：SRSF3 ; PDCD4 ; Alterative splicing ; Export ; Translation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2016
• 出版时间：5 February 2016
• 年：2016
• 卷：470
• 期：2
• 页码：431-438
• 全文大小：820 K

文摘

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.