PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells.
PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells.
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PTBP1和PTBP2损害癌细胞中SRSF3的自动调节
DOI：
10.1038/srep14548
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发表时间：
2015-09-29
影响因子：
4.6
通讯作者：
Jia R
中科院分区：
文献类型：
--
作者：
Guo J;Jia J;Jia R
剪接因子是调控pre- mrna选择性剪接的关键因素。包括SRSF3在内的剪接因子的过表达与肿瘤的发生密切相关。然而，它们过度表达背后的机制在很大程度上仍不清楚。自调节是维持剪接因子在细胞中相对稳定表达水平的一种常见机制。SRSF3通过增强包含具有帧内停止密码子的替代外显子4来调节其自身的表达。我们发现SRSF3外显子4在口腔鳞状细胞癌（OSCC）细胞中受损。PTBP1和PTBP2与外显子4的剪接抑制子结合并抑制其包含，导致全长功能性SRSF3过表达。SRSF3的过表达反过来促进PTBP2的表达。我们的研究结果提示了致癌剪接因子的过度表达在癌细胞中损害自身调节的新机制。
Splicing factors are key players in the regulation of alternative splicing of pre-mRNAs. Overexpression of splicing factors, including SRSF3, has been strongly linked with oncogenesis. However, the mechanisms behind their overexpression remain largely unclear. Autoregulation is a common mechanism to maintain relative stable expression levels of splicing factors in cells. SRSF3 regulates its own expression by enhancing the inclusion of an alternative exon 4 with an in-frame stop codon. We found that the inclusion of SRSF3 exon 4 is impaired in oral squamous cell carcinoma (OSCC) cells. PTBP1 and PTBP2 bind to an exonic splicing suppressor in exon 4 and inhibit its inclusion, which results in overexpression of full length functional SRSF3. Overexpression of SRSF3, in turn, promotes PTBP2 expression. Our results suggest a novel mechanism for the overexpression of oncogenic splicing factorviaimpairing autoregulation in cancer cells.