SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs

被引:252
作者
Sureau, A
Gattoni, R
Dooghe, Y
Stévenin, J
Soret, J
机构
[1] Ctr Univ Orsay, CNRS, Inst Curie, UMR 146, F-91405 Orsay, France
[2] CNRS, Ctr Genet Mol, UPR 2167, F-91190 Gif Sur Yvette, France
[3] ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, France
关键词
alternative splicing; autoregulation; mRNA stability; SC35;
D O I
10.1093/emboj/20.7.1785
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1785 / 1796
页数:12
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