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TIA1
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<h2 id="function">Function</h2> <p>This protein is a member of a RNA-binding protein family that regulates <a href="/facts/Transcription_(biology)/bDgp9HDN">transcription</a> and <a href="/facts/RNA_translation/JcPC1rth">RNA translation</a>. It was first identified in cytotoxic lymphocyte (CTL) target cells. TIA1 acts in the nucleus to regulate splicing and transcription.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> TIA1 helps to recruit the splicesome to regulate RNA splicing, and it inhibits transcription of multiple genes, such as the cytokine <a href="/facts/Tumor_necrosis_factor_alpha/7NWNIaCb">Tumor necrosis factor alpha</a>.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> In response to stress, TIA1 translocates from the nucleus to the cytoplasm, where it nucleates a type of RNA granule, termed the <a href="/facts/Stress_granule/VPBUcM3f">stress granule</a>, and participates in the translational stress response.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> 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.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> 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.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> 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. </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Stress_granule/VPBUcM3f">Stress granule</a></li> <li><a href="/facts/T-cell_large_granular_lymphocyte_leukemia/LwDK0aHT">T-cell large granular lymphocyte leukemia</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Kawakami A, Tian Q, Streuli M, Poe M, Edelhoff S, Disteche CM, Anderson P (May 1994). <a href="https://doi.org/10.4049%2Fjimmunol.152.10.4937">"Intron-exon organization and chromosomal localization of the human TIA-1 gene"</a>. <i>Journal of Immunology</i>. 152 (10): 4937–45. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.4049%2Fjimmunol.152.10.4937">10.4049/jimmunol.152.10.4937</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8176212">8176212</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:24031486">24031486</a>.</li> <li>Dember LM, Kim ND, Liu KQ, Anderson P (February 1996). <a href="https://doi.org/10.1074%2Fjbc.271.5.2783">"Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities"</a>. <i>The Journal of Biological Chemistry</i>. 271 (5): 2783–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.271.5.2783">10.1074/jbc.271.5.2783</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8576255">8576255</a>.</li> <li>Bossowski A, Czarnocka B, Bardadin K, Moniuszko A, Łyczkowska A, Czerwinska J, et al. (January 2010). <a href="https://doi.org/10.2478%2Fv10042-010-0022-2">"Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid tissues from adolescents with immune and non-immune thyroid diseases"</a>. <i>Folia Histochemica et Cytobiologica</i>. 48 (2): 178–84. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2478%2Fv10042-010-0022-2">10.2478/v10042-010-0022-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/20675271">20675271</a>.</li> <li>Aznarez I, Barash Y, Shai O, He D, Zielenski J, Tsui LC, et al. (August 2008). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493427">"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"</a>. <i>Genome Research</i>. 18 (8): 1247–58. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1101%2Fgr.073155.107">10.1101/gr.073155.107</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493427">2493427</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/18456862">18456862</a>.</li> <li>López de Silanes I, Galbán S, Martindale JL, Yang X, Mazan-Mamczarz K, Indig FE, et al. (November 2005). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265820">"Identification and functional outcome of mRNAs associated with RNA-binding protein TIA-1"</a>. <i>Molecular and Cellular Biology</i>. 25 (21): 9520–31. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2FMCB.25.21.9520-9531.2005">10.1128/MCB.25.21.9520-9531.2005</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265820">1265820</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16227602">16227602</a>.</li> <li>McAlinden A, Liang L, Mukudai Y, Imamura T, Sandell LJ (August 2007). <a href="https://doi.org/10.1074%2Fjbc.M702717200">"Nuclear protein TIA-1 regulates COL2A1 alternative splicing and interacts with precursor mRNA and genomic DNA"</a>. <i>The Journal of Biological Chemistry</i>. 282 (33): 24444–54. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M702717200">10.1074/jbc.M702717200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17580305">17580305</a>.</li> <li>Anderson P, Nagler-Anderson C, O'Brien C, Levine H, Watkins S, Slayter HS, et al. (January 1990). <a href="https://doi.org/10.4049%2Fjimmunol.144.2.574">"A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes"</a>. <i>Journal of Immunology</i>. 144 (2): 574–82. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.4049%2Fjimmunol.144.2.574">10.4049/jimmunol.144.2.574</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2104899">2104899</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:6152276">6152276</a>.</li> <li>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". <i>Arthritis and Rheumatism</i>. 56 (7): 2160–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fart.22724">10.1002/art.22724</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17599736">17599736</a>.</li> <li>Singh NN, Seo J, Ottesen EW, Shishimorova M, Bhattacharya D, Singh RN (March 2011). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067828">"TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy"</a>. <i>Molecular and Cellular Biology</i>. 31 (5): 935–54. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2FMCB.00945-10">10.1128/MCB.00945-10</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067828">3067828</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/21189287">21189287</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=TIA1+protein%2C+human">TIA1+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Izquierdo JM, Majós N, Bonnal S, Martínez C, Castelo R, Guigó R, et al. (August 2005). "Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition". Molecular Cell. 19 (4): 475–84. doi:10.1016/j.molcel.2005.06.015. PMID 16109372. <a href="https://doi.org/10.1016%2Fj.molcel.2005.06.015" target="_blank">https://doi.org/10.1016%2Fj.molcel.2005.06.015</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Kedersha NL, Gupta M, Li W, Miller I, Anderson P (December 1999). "RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules". The Journal of Cell Biology. 147 (7): 1431–42. doi:10.1083/jcb.147.7.1431. PMC 2174242. PMID 10613902. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174242" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174242</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: TIA1 cytotoxic granule-associated RNA binding protein". <a href="https://www.ncbi.nlm.nih.gov/gene/7072" target="_blank">https://www.ncbi.nlm.nih.gov/gene/7072</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, et al. (August 2017). "TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics". Neuron. 95 (4): 808–816.e9. doi:10.1016/j.neuron.2017.07.025. PMC 5576574. PMID 28817800. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576574" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576574</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Ash PE, Lei S, Shattuck J, Boudeau S, Carlomagno Y, Medalla M, et al. (March 2021). "TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau". Proceedings of the National Academy of Sciences of the United States of America. 118 (9): e2014188118. Bibcode:2021PNAS..11814188A. doi:10.1073/pnas.2014188118. PMC 7936275. PMID 33619090. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936275" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936275</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Rayman JB, Kandel ER (May 2017). "TIA-1 Is a Functional Prion-Like Protein". Cold Spring Harbor Perspectives in Biology. 9 (5): a030718. doi:10.1101/cshperspect.a030718. PMC 5411700. PMID 28003185. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411700" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411700</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Rayman JB, Kandel ER (May 2017). "TIA-1 Is a Functional Prion-Like Protein". Cold Spring Harbor Perspectives in Biology. 9 (5): a030718. doi:10.1101/cshperspect.a030718. PMC 5411700. PMID 28003185. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411700" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411700</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Anderson P, Kedersha N (March 2008). "Stress granules: the Tao of RNA triage". Trends in Biochemical Sciences. 33 (3): 141–50. doi:10.1016/j.tibs.2007.12.003. PMID 18291657. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Wolozin B, Ivanov P (November 2019). "Stress granules and neurodegeneration". Nature Reviews. Neuroscience. 20 (11): 649–666. doi:10.1038/s41583-019-0222-5. PMC 6986315. PMID 31582840. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986315" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986315</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Anderson P, Kedersha N, Ivanov P (July 2015). "Stress granules, P-bodies and cancer". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1849 (7): 861–70. doi:10.1016/j.bbagrm.2014.11.009. PMC 4457708. PMID 25482014. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457708" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457708</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> </ol>