TIA-1 and TIAR activate splicing of alternative exons with weak 5 ' splicesites followed by a U-rich stretch on their own pre-mRNAs

TIA-1 has recently been shown to activate splicing of specific pre-mRNAs tr anscribed from transiently transfected minigenes, and of some 5' splice sit es in vitro, but has not been shown to activate splicing of any endogenous pre-mRNA. We show here that overexpression of TIA-1 or the related protein TIAR has little effect on splicing of several endogenous pre-mRNAs containi ng alternative exons, but markedly activates splicing of some normally rare ly used alternative exons on the TIA-1 and TIAR pre-mRNAs. These exons have weak 5' splice sites followed by U-rich stretches. When the U-rich stretch following the 5' splice site of a TIA-1 alternative exon was deleted, TIAR overexpression induced use of a cryptic 5' splice site also followed by a U-rich stretch in place of the original splice site. Using in vitro splicin g assays, we have shown that TIA-1 is directly involved in activating the 5 ' splice sites of the TIAR, alternative exons. Activation requires a downst ream U-rich stretch of at least 10 residues. Our results confirm that TIA-1 activates 5' splice sites followed by U-rich sequences and show that TIAR exerts a similar activity. They suggest that both proteins may autoregulate their expression at the level of splicing.