The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing

Patrik Förch, Oscar Puig, Nancy Kedersha, Concepción Martínez, Sander Granneman, Bertrand Séraphin, Paul Anderson, Juan Valcárcel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We report here that the apoptosis-promoting protein TIA-1 regulates alternative pre-mRNA splicing of the Drosophila melanogaster gene male-specific-lethal 2 and of the human apoptotic gene Fas. TIA-1 associates selectivity with pre-mRNAs that contain 5' splice sites followed by U-rich sequences. TIA-1 binding to the U-rich stretches facilitates 5' splice site recognition by U1 snRNP. This activity is critical for activation of the weak 5' splice site of msl-2 and for modulating the choice of splice site partner in Fas. Structural and functional similarities with the Saccharomyces cerevisiae splicing factor Nam8 suggest striking evolutionary conservation of a mechanism of pre-mRNA splicing regulation that controls biological processes as diverse as meiosis in yeast, dosage compensation in fruit flies, or programmed cell death in humans.

Original languageEnglish
Pages (from-to)1089-1098
Number of pages10
JournalMolecular Cell
Volume6
Issue number5
DOIs
Publication statusPublished - 2000

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