Molecular mechanisms of gene expression regulation by the apoptosis-promoting protein TIA-1

TIA-1 and the related protein TIAR promote DNA fragmentation in digitonin-p ermeabilized thymocytes. These proteins contain RNA Recognition Motifs (RRM s) and bind uridine-rich sequences. These observations suggested that TIA-1 /TIAR are pro-apoptotic factors that influence some aspect of RNA metabolis m. Here we review recent data implicating TIA-1 as a regulator of translati on of Tumor Necrosis Factor-alpha mRNA and as regulator of alternative spli cing of a variety of pre-mRNAs, including those of the Fibroblast Growth Fa ctor Receptor 2 and the Fas receptor. We also discuss how some of these act ivities could be integrated in the control of programmed of cell death.