SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs
SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs
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DOI：
10.1093/emboj/20.7.1785
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发表时间：
2001-04-02
期刊：
影响因子：
11.4
通讯作者：
Soret, J
中科院分区：
文献类型：
--
作者：
Sureau, A;Gattoni, R;Soret, J
SC35 属于 SR 蛋白家族，在体外和体内以浓度依赖性方式调节选择性剪接。我们之前报道过 SC35 通过具有不同 3' 非翻译序列和稳定性的选择性剪接 mRNA 表达。在这里，我们发现 HeLa 细胞中 SC35 的过度表达导致内源 SC35 mRNA 水平显着降低，同时 SC35 选择性剪接 mRNA 的相对丰度发生变化。值得注意的是，SC35 导致其 mRNA 3' 非翻译区出现外显子包含和内含子切除。使用重组 SR 蛋白进行的体外剪接实验表明，SC35（而非 ASF/SF2 或 9G8）特异性激活这些选择性剪接事件。有趣的是，由此产生的 mRNA 非常不稳定，我们提供的证据表明 mRNA 监视可能与这种不稳定有关。因此，SC35 构成了剪接因子的第一个例子，该剪接因子通过激活剪接事件导致不稳定 mRNA 的表达来控制其自身表达。
SC35 belongs to the family of SR proteins that regulate alternative splicing in a concentration-dependent manner in vitro and in vivo. We previously reported that SC35 is expressed through alternatively spliced mRNAs with differing 3' untranslated sequences and stabilities. Here, we show that overexpression of SC35 in HeLa cells results in a significant decrease of endogenous SC35 mRNA levels along with changes in the relative abundance of SC35 alternatively spliced mRNAs. Remarkably, SC35 leads to both an exon inclusion and an intron excision in the 3' untranslated region of its mRNAs. In vitro splicing experiments performed with recombinant SR proteins demonstrate that SC35, but not ASF/SF2 or 9G8, specifically activates these alternative splicing events. Interestingly, the resulting mRNA is very unstable and we present evidence that mRNA surveillance is likely to be involved in this instability. SC35 therefore constitutes the first example of a splicing factor that controls its own expression through activation of splicing events leading to expression of unstable mRNA.