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

Mol Cell. 2000 Nov;6(5):1089-98. doi: 10.1016/s1097-2765(00)00107-6.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Apoptosis*
  • Base Sequence
  • Binding Sites
  • Conserved Sequence
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Drosophila melanogaster / genetics
  • Fibroblasts
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • HeLa Cells
  • Humans
  • Introns / genetics
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Poly(A)-Binding Proteins
  • Protein Binding
  • Proteins*
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Splice Sites / genetics
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease H / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / metabolism
  • Ribonucleoproteins / metabolism
  • Ribonucleoproteins, Small Nuclear*
  • Saccharomyces cerevisiae Proteins*
  • Splicing Factor U2AF
  • Substrate Specificity
  • T-Cell Intracellular Antigen-1
  • Transcription Factors / genetics
  • fas Receptor / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Fungal Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Poly(A)-Binding Proteins
  • Proteins
  • RNA Precursors
  • RNA Splice Sites
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • Splicing Factor U2AF
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • Transcription Factors
  • U2AF2 protein, human
  • fas Receptor
  • msl-2 protein, Drosophila
  • NAM8 protein, S cerevisiae
  • Ribonuclease H