Spliced to Kill

Abstract

One mechanism for regulating protein activity is to create a different protein by alternative splicing. Förch et al. isolated TIA-1 as a cellular factor that could be crosslinked to Drosophila male-specific-lethal 2 ( msl-2 ) pre-mRNA and that was required for efficient splicing of msl-2 . TIA-1 binding was dependent on two poly-uridine tracts in the 5' splice-site region. Database searching revealed that human Fas pre-mRNA has a similar sequence at the 5' splice site of exon 6, which is alternatively spliced to produce proteins that contain the exon 6 sequence and are pro-apoptotic or that lack the exon 6 sequence and inhibit apoptosis. TIA-1 bound to the 5' splice site of Fas exon 6 and promoted inclusion of exon 6 from a minigene expressed in mouse fibroblast cell lines. These data provide a mechanism for the pro-apoptotic effects of TIA-1. TIA-1 and the related protein TIAR are known to translocate from the nucleus to the cytosol and are phosphorylated during Fas-mediated cell death. Thus, this may be yet another layer to the complex regulatory pathway that governs apoptosis. Förch, P., Puig, O., Kedersha, N., Martínez, C., Granneman, S., Séraphin, B., Anderson, P., and Valcárcel, J. (2000) The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing. Mol. Cell 6 : 1089-1098. [Online Journal]