TIA1

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]

TIA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MJN, 3BS9
Identifiers
Aliases	TIA1, TIA-1, WDM, TIA1 cytotoxic granule-associated RNA binding protein, TIA1 cytotoxic granule associated RNA binding protein
External IDs	OMIM: 603518 MGI: 107914 HomoloGene: 20692 GeneCards: TIA1
Gene location (Mouse) Chr. Chromosome 6 (mouse)[1] Band 6|6 D1 Start 86,404,219 bp[1] End 86,433,405 bp[1]
Gene ontology Molecular function • nucleic acid binding • GO:0001948 protein binding • AU-rich element binding • poly(A) binding • RNA binding • mRNA 3'-UTR AU-rich region binding Cellular component • cytoplasm • Stress granule • nuclear stress granule • cell nucleus • nucleoplasm • cytosol • ribonucleoprotein Biological process • negative regulation of cytokine biosynthetic process • negative regulation of translation • positive regulation of epithelial cell apoptotic process • regulation of mRNA splicing, via spliceosome • protein localization to cytoplasmic stress granule • apoptotic process • fibroblast growth factor receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7072	21841
Ensembl	ENSG00000116001	ENSMUSG00000071337
UniProt	P31483	P52912
RefSeq (mRNA)	NM_022037 NM_022173	NM_001164078 NM_001164079 NM_011585
RefSeq (protein)	NP_071320 NP_071505 NP_001338437 NP_001338438 NP_001338439 NP_001338440 NP_001338441 NP_001338443 NP_001338444 NP_001338445 NP_001338446 NP_001338447 NP_001338448 NP_001338449 NP_001338450 NP_001338451 NP_001338452 NP_001338453 NP_001338454 NP_001338442	NP_001157550 NP_001157551 NP_035715
Location (UCSC)	n/a	Chr 6: 86.4 – 86.43 Mb
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

TIA1 (protein)
Identifiers
Symbol	TIA1
NCBI gene	7072
HGNC	11802
OMIM	603518
RefSeq	NM_022173
UniProt	P31483
Other data
Locus	Chr. 2 p13
Search for Structures Swiss-model Domains InterPro

Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy.[7][8][9]

Function

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.[10] 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 [10] 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.[11] 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.[12] 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.[13] 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.

See also

• Stress granule
• T-cell large granular lymphocyte leukemia

References

1. GRCm38: Ensembl release 89: ENSMUSG00000071337 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. 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.
5. 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.
6. "Entrez Gene: TIA1 cytotoxic granule-associated RNA binding protein".
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.

Further reading

• 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. PMID 8176212.
• 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. PMID 2104899.
• 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.

External links

• TIA1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.