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

SC35 belongs to the family of SR proteins that regulate alternative splicin g in a concentration-dependent manner in vitro and in vivo. We previously r eported that SC35 is expressed through alternatively spliced mRNAs with dif fering 3' untranslated sequences and stabilities. Here, we show that overex pression of SC35 in HeLa cells results in a significant decrease of endogen ous SC35 mRNA levels along with changes in the relative abundance of SC35 a lternatively spliced mRNAs. Remarkably, SC35 leads to both an exon inclusio n and an intron excision in the 3' untranslated region of its mRNAs. In vit ro 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 i nstability. SC35 therefore constitutes the first example of a splicing fact or that controls its own expression through activation of splicing events l eading to expression of unstable mRNA.