TIA1

Description

The TIA1 (TIA1 cytotoxic granule associated RNA binding protein) is a protein-coding gene located on chromosome 2.

TIA1, or Tia1 cytotoxic granule-associated RNA binding protein, is a 3'UTR mRNA binding protein that can bind the 5'TOP sequence of 5'TOP mRNAs. It is associated with programmed cell death (apoptosis) and regulates alternative splicing of the gene encoding the Fas receptor, an apoptosis-promoting protein. Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules. It is encoded by the TIA1 gene. Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy. It also plays a crucial role in the development of toxic oligomeric tau in Alzheimer's disease. This protein is a member of a RNA-binding protein family that regulates transcription and RNA translation. It was first identified in cytotoxic lymphocyte (CTL) target cells. TIA1 acts in the nucleus to regulate splicing and transcription. TIA1 helps to recruit the splicesome to regulate RNA splicing, and it inhibits transcription of multiple genes, such as the cytokine Tumor necrosis factor alpha.

RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences. It binds to U-rich sequences immediately downstream from a 5' splice site in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing. It preferentially binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner, with optimal binding when a 5' splice site is adjacent to IAS1. It activates the use of heterologous 5' splice sites, with activation dependent on the intron sequence downstream from the 5' splice site, favoring a downstream U-rich sequence. By interacting with SNRPC/U1-C, it 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. It 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. It acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis. It 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, leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis. It binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2. It also binds to the equivalent AT-rich element in COL2A1 genomic DNA, potentially playing a role in the regulation of transcription. It 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, antagonizing PTB1 and its role in exon skipping of CFTR exon 9. It is 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. It also participates in the cellular response to environmental stress, 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+). It possesses nucleolytic activity against cytotoxic lymphocyte target cells.

TIA1 is also known as ALS26, TIA-1, WDM.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing