The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing.
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 selectively 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.
Förch
P
P
Gene Expression Programme European Molecular Biology Laboratory Meyerhofstrasse 1 D-69117, Heidelberg, Germany.
Puig
O
O
Kedersha
N
N
Martínez
C
C
Granneman
S
S
Séraphin
B
B
Anderson
P
P
Valcárcel
J
J
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D005347:Fibroblasts; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D039102:Poly(A)-Binding Proteins; D011485:Protein Binding; D011506:Proteins; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016914:Ribonuclease H / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D000072668:Splicing Factor U2AF; D013379:Substrate Specificity; D000074019:T-Cell Intracellular Antigen-1; D014157:Transcription Factors / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D012322:RNA Precursors; D022821:RNA Splice Sites; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D000072668:Splicing Factor U2AF; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D014157:Transcription Factors; C000607494:U2AF2 protein, human; D019014:fas Receptor; C094166:msl-2 protein, Drosophila; C075023:NAM8 protein, S cerevisiae; D016914:Ribonuclease H