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.[4] Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules.[5] It is encoded by the TIA1 gene.[6]
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Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy.[7][8][9] It also plays a crucial role in the development of toxic oligomeric tau in Alzheimer's disease.[10]
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.[11] 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.[11] In response to stress, TIA1 translocates from the nucleus to the cytoplasm, where it nucleates a type of RNA granule, termed the stress granule, and participates in the translational stress response.[12] As part of the translational stress response, TIA1 works in cooperation with other RNA binding proteins to sequester RNA transcripts away from the ribosome, which allows the cell to focus its protein synthesis/RNA translation machinery on producing proteins that will address the particular stress.[13] It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets.[14] The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms of this gene product have been described.
Hackman P, Sarparanta J, Lehtinen S, Vihola A, Evilä A, Jonson PH, et al. (April 2013). "Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1". Annals of Neurology. 73 (4): 500–9. doi:10.1002/ana.23831. PMID 23401021. S2CID 13908127.
Klar J, Sobol M, Melberg A, Mäbert K, Ameur A, Johansson AC, et al. (April 2013). "Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing". Human Mutation. 34 (4): 572–7. doi:10.1002/humu.22282. PMID 23348830. S2CID 10955236.
- Kawakami A, Tian Q, Streuli M, Poe M, Edelhoff S, Disteche CM, Anderson P (May 1994). "Intron-exon organization and chromosomal localization of the human TIA-1 gene". Journal of Immunology. 152 (10): 4937–45. doi:10.4049/jimmunol.152.10.4937. PMID 8176212. S2CID 24031486.
- Dember LM, Kim ND, Liu KQ, Anderson P (February 1996). "Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities". The Journal of Biological Chemistry. 271 (5): 2783–8. doi:10.1074/jbc.271.5.2783. PMID 8576255.
- Bossowski A, Czarnocka B, Bardadin K, Moniuszko A, Łyczkowska A, Czerwinska J, et al. (January 2010). "Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid tissues from adolescents with immune and non-immune thyroid diseases". Folia Histochemica et Cytobiologica. 48 (2): 178–84. doi:10.2478/v10042-010-0022-2. PMID 20675271.
- Aznarez I, Barash Y, Shai O, He D, Zielenski J, Tsui LC, et al. (August 2008). "A systematic analysis of intronic sequences downstream of 5' splice sites reveals a widespread role for U-rich motifs and TIA1/TIAL1 proteins in alternative splicing regulation". Genome Research. 18 (8): 1247–58. doi:10.1101/gr.073155.107. PMC 2493427. PMID 18456862.
- López de Silanes I, Galbán S, Martindale JL, Yang X, Mazan-Mamczarz K, Indig FE, et al. (November 2005). "Identification and functional outcome of mRNAs associated with RNA-binding protein TIA-1". Molecular and Cellular Biology. 25 (21): 9520–31. doi:10.1128/MCB.25.21.9520-9531.2005. PMC 1265820. PMID 16227602.
- McAlinden A, Liang L, Mukudai Y, Imamura T, Sandell LJ (August 2007). "Nuclear protein TIA-1 regulates COL2A1 alternative splicing and interacts with precursor mRNA and genomic DNA". The Journal of Biological Chemistry. 282 (33): 24444–54. doi:10.1074/jbc.M702717200. PMID 17580305.
- Anderson P, Nagler-Anderson C, O'Brien C, Levine H, Watkins S, Slayter HS, et al. (January 1990). "A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes". Journal of Immunology. 144 (2): 574–82. doi:10.4049/jimmunol.144.2.574. PMID 2104899. S2CID 6152276.
- Sugihara M, Tsutsumi A, Suzuki E, Wakamatsu E, Suzuki T, Ogishima H, et al. (July 2007). "Effects of infliximab therapy on gene expression levels of tumor necrosis factor alpha, tristetraprolin, T cell intracellular antigen 1, and Hu antigen R in patients with rheumatoid arthritis". Arthritis and Rheumatism. 56 (7): 2160–9. doi:10.1002/art.22724. PMID 17599736.
- Singh NN, Seo J, Ottesen EW, Shishimorova M, Bhattacharya D, Singh RN (March 2011). "TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy". Molecular and Cellular Biology. 31 (5): 935–54. doi:10.1128/MCB.00945-10. PMC 3067828. PMID 21189287.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.