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M105642200v1
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Papers In Press, published online ahead of print August 20, 2001
J. Biol. Chem, 10.1074/jbc.M105642200
Submitted on June 19, 2001
Revised on August 13, 2001
Accepted on August 19, 2001

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

Caroline Le Guiner, Fabrice Lejeune, Delphine Galiana, Liliane Kister, Richard Breathnach, James Stévenin, and Fabienne Del Gatto-Konczak

Institut de Biologie-CHR, INSERM U463, 44093, Nantes Cedex 1

Corresponding Author: fdelgatto{at}nantes.inserm.fr

TIA-1 has recently been shown to activate splicing of specific pre-mRNAs transcribed from transiently transfected minigenes, and of some 5' splice sites 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 containing alternative exons, but markedly activates splicing of some normally rarely 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 splicing assays, we have shown that TIA-1 is directly involved in activating the 5' splice sites of the TIAR alternative exons. Activation requires a downstream 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.


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