TIA1

TIA1 ili Tia1 RNK-citotoksičnim granulama pridruženi vezivni protein jest protein koji je kod ljudi kodiran genom sa hromosoma 2. To je 3' UTR iRNK vezujući protein koji može vezati 5'TOP sekvencu 5'TOP iRNK. Povezan je sa programiranom smrću ćelija (apoptoza) i regulira alternativnu preradu gena koji kodira Fas receptor, protein koji podstiče apoptozu.^[4] U uslovima stresa, TIA1 nalazi se na ćelijskoj konglomeraciji RNK – protein zvanoj stresna granula.^[5] Kodira je TIA1 gen.^[6]

TIA1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 2MJN, 3BS9
Identifikatori
Aliasi	TIA1
Vanjski ID-jevi	OMIM: 603518 MGI: 107914 HomoloGene: 20692 GeneCards: TIA1
Lokacija gena (miš) Hrom. Hromosom 6 (miš)[1] Bend 6|6 D1 Početak 86,381,201 bp[1] Kraj 86,410,387 bp[1]
Ontologija gena Molekularna funkcija • nucleic acid binding • GO:0001948 protein binding • poly(A) binding • RNA binding • mRNA 3'-UTR AU-rich region binding Ćelijska komponenta • citoplazma • cytoplasmic stress granule • nuclear stress granule • Jedro • Nukleoplazma • citosol • Ribonukleoprotein Biološki proces • negative regulation of translation • positive regulation of epithelial cell apoptotic process • regulation of mRNA splicing, via spliceosome • protein localization to cytoplasmic stress granule • Apoptoza • fibroblast growth factor receptor signaling pathway Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	7072	21841
Ensembl	ENSG00000116001	ENSMUSG00000071337
UniProt	P31483	P52912
RefSeq (mRNK)	NM_022037 NM_022173	NM_001164078 NM_001164079 NM_011585
RefSeq (bjelančevina)	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
Lokacija (UCSC)	n/a	Chr 6: 86.38 – 86.41 Mb
PubMed pretraga	[2]	[3]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

[Mutacije]] u genu "TIA1" povezane su sa amiotrofnom lateralnom sklerozom, frontotemporalnom demencijom i Welanderovom distalnaom miopatijom.^[7][8][9] Također ima ključnu ulogu u razvoju toksičnog oligomernog tau proteina kod Alzheimerove bolesti.^[10]

Funkcija

Ovaj protein je član porodice proteina koji se vezuje za RNK i reguliše transkripciju i translaciju RNK. Prvo je identificiran u ciljnim ćelijama citotoksičnih limfocita (CTL). TIA1 djeluje u jedru da regulira preradu i transkripciju.^[11] TIA1 pomaže da se regrutuje spoj za regulaciju prerade RNK i inhibira transkripciju više gena, kao što je citokinski faktor nekroze tumora alfa.^[11] Kao odgovor na stres, TIA1 se translocira iz jedra u citoplazmu, gdje stvara jedro tipa RNK granula, zvanog stresne granule, i sudjeluje u translacijskom odgovoru na stres.^[12] Kao dio translacijskog odgovora na stres, TIA1 djeluje u suradnji s drugim proteinima koji se vezuju za RNK, kako bi sekvestrirao transkripte RNK od ribosoma, što omogućava ćeliji da fokusira svoju sintezu proteina/mehanizam za translaciju RNK na proizvodnju proteina koji će se baviti određenim stresom.^[13] Pretpostavlja se da ovaj protein može biti uključen u indukciju apoptoza, jer preferencijalno prepoznaje poli(A) homopolimere i inducira fragmentaciju DNK u CTL metama.^[14] Glavna vrsta povezana sa granulama je protein od 15 kDa, za koji se smatra da je izveden iz karboksilnog kraja proizvoda od 40 kDa proteolitskom obradom. Opisana je alternativna prerada koje rezultira različitim izoformama ovog genskog proizvoda.

Također pogledajte

• Stresna granula
• T-ćelijska leukemija velikih granuliranih limfocita

Reference

1. GRCm38: Ensembl release 89: ENSMUSG00000071337 - Ensembl, maj 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. 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. doi:10.1073/pnas.2014188118. PMC 7936275. PMID 33619090.
11. 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.
12. 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.
13. 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.
14. 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.

Dopunska literatura

• 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.

Vanjski linkovi

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

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.