Protein: Cytotoxic granule associated RNA binding protein TIA1 (Nucleolysin TIA-1 isoform p40) (RNA-binding protein TIA-1) (T-cell-restricted intracellular antigen-1) (TIA-1) (p40-TIA-1) (P31483)
Organism: Homo sapiens (Human)
Function: RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences. Binds to U-rich sequences immediately downstream from a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing. Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is optimal if a 5' splice site is adjacent to IAS1 (By similarity). Activates the use of heterologous 5' splice sites; the activation depends on the intron sequence downstream from the 5' splice site, with a preference for a downstream U-rich sequence. By interacting with SNRPC/U1-C, promotes recruitment and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences, thereby facilitating atypical 5' splice site recognition by U1 snRNP. Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIAR mRNA (By similarity). Acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis. Binds to the 5' splice site region of FAS intron 5 to promote accumulation of transcripts that include exon 6 at the expense of transcripts in which exon 6 is skipped, thereby leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis. Binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2. Also binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby be involved in the regulation of transcription. Binds specifically to a polypyrimidine-rich controlling element (PCE) located between the weak 5' splice site and the intronic splicing silencer of CFTR mRNA to promote exon 9 inclusion, thereby antagonizing PTB1 and its role in exon skipping of CFTR exon 9. Involved in the repression of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs), including target ARE-bearing mRNAs encoding TNF and PTGS2 (By similarity). Also participates in the cellular response to environmental stress, by acting downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs), leading to stress-induced translational arrest. Formation and recruitment to SGs is regulated by Zn(2+) (By similarity). Possesses nucleolytic activity against cytotoxic lymphocyte target cells.
Subcellular location: Nucleus {ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:15371533, ECO:0000269|PubMed:17984221, ECO:0000305|PubMed:18201561}. Cytoplasm {ECO:0000269|PubMed:17488725}. Cytoplasm, Stress granule {ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:15371533, ECO:0000269|PubMed:17984221}. Note=Accumulates in cytoplasmic stress granules (SG) following cellular damage (PubMed:10613902, PubMed:15371533). Recruitment to SG is induced by Zn(2+) (By similarity). {ECO:0000250|UniProtKB:P52912, ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:15371533}.
Interaction partners:
- Ras GTPase-activating protein-binding protein 1
- Nucleolysin TIAR
- U1 small nuclear ribonucleoprotein C
- ELAV-like protein 1
- Eukaryotic translation initiation factor 4 gamma 1
- Eukaryotic translation initiation factor 4E
- Polyadenylate-binding protein 1
- TAR DNA-binding protein 43
- Poly
- Ataxin-2
Sequence:
MEDEMPKTLYVGNLSRDVTEALILQLFSQIGPCKNCKMIMDTAGNDPYCFVEFHEHRHAAAALAAMNGRKIMGKEVKVNWATTPSSQKKDTSSSTVVSTQRSQDHFHVFVGDLSPEITTEDIKAAFAPFGRISDARVVKDMATGKSKGYGFVSFFNKWDAENAIQQMGGQWLGGRQIRTNWATRKPPAPKSTYESNTKQLSYDEVVNQSSPSNCTVYCGGVTSGLTEQLMRQTFSPFGQIMEIRVFPDKGYSFVRFNSHESAAHAIVSVNGTTIEGHVVKCYWGKETLDMINPVQQQNQIGYPQPYGQWGQWYGNAQQIGQYMPNGWQVPAYGMYGQAWNQQGFNQTQSSAPWMGPNYGVQPPQGQNGSMLPNQPSGYRVAGYETQ