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Gene Review

TIAL1  -  TIA1 cytotoxic granule-associated RNA...

Homo sapiens

Synonyms: Nucleolysin TIAR, TCBP, TIA-1-related protein, TIAR
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Disease relevance of TIAL1


Psychiatry related information on TIAL1

  • Using a monoclonal antibody against TIAR, we stained different areas of the hippocampus from seven controls and 14 patients with Alzheimer's disease (AD) [5].
  • Several factors, such as animal behavior and TCBP water solubility limitations, were evaluated to explain the concentration effect, but the most likely cause was severe diffusion limitations in whole sediment that were not predicted by the fully mixed Tenax extraction [6].

High impact information on TIAL1

  • (2007) reported that the steroid receptor coactivator-3 (SRC-3) has a novel cytoplasmic function: it activates the translational silencers TIA-1 and TIAR and thus inhibits the translation of proinflammatory cytokines [7].
  • After genotoxic stress, AUF1 and TIAR dissociated from the GADD45alpha mRNA, thereby allowing coordinated elevations in both GADD45alpha mRNA half-life and translation rate, respectively [8].
  • Analysis of both endogenous and chimeric GADD45alpha mRNA revealed that in untreated cells AUF1 strongly reduced GADD45alpha mRNA stability, whereas TIAR potently inhibited GADD45alpha translation [8].
  • Here, two RNA binding proteins, the mRNA decay-promoting AUF1 and the translational suppressor TIAR, were found to interact specifically with the 3' untranslated region (UTR) of the GADD45alpha mRNA in HeLa cells [8].
  • Transgenic overexpression of TIAR during SeV infection promotes apoptosis and reverses the anti-apoptotic effects of le* RNA expression [1].

Biological context of TIAL1

  • Consistent with this possibility, we have found that the expression and intracellular localization of TIAR change dramatically during Fas-mediated apoptosis [9].
  • The RNA-binding protein TIAR is translocated from the nucleus to the cytoplasm during Fas-mediated apoptotic cell death [9].
  • Redistribution of TIAR precedes the onset of DNA fragmentation and is not a nonspecific consequence of nuclear disintegration [9].
  • The deduced amino acid sequence of TIAR reveals it to be a 42-kDa protein possessing three RNA-binding domains and a carboxyl-terminal auxiliary domain [10].
  • We have determined the structure, intracellular localization, and tissue distribution of TIAR, a TIA-1-related RNA-binding protein [9].

Anatomical context of TIAL1

  • Unlike TIA-1, which is found in the granules of cytotoxic lymphocytes, TIAR is concentrated in the nucleus of hematopoietic and nonhematopoietic cells [9].
  • This stress-induced scarcity of eIF2-GTP-tRNA(Met) allows the RNA-binding proteins TIA-1 (T-cell internal antigen-1) and TIAR (TIA-1-related protein) to bind the 48 S complex in lieu of the ternary complex, thereby promoting polysome disassembly and the concurrent routing of the mRNA into a SG [11].
  • Furthermore, we identified two RNA-binding proteins, HuR and the T-cell-restricted intracellular antigen 1-related protein (TIAR), which were associated with endogenous COX-2 mRNA in 308 keratinocytes, and apigenin treatment increased their localization to cell cytoplasm [12].
  • WNV growth was less efficient in murine TIAR knockout cell lines than in control cells [2].
  • T-cell restricted intracellular antigen-related protein (TIAR) is an RNA recognition motif-type RNA-binding protein that has been implicated in the apoptotic death of T-lymphocytes and retinal pigment epithelial cells [4].

Associations of TIAL1 with chemical compounds

  • TIA-1 related protein binds avidly to uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF) [13].
  • We show by ultraviolet crosslinking and electrophoretic mobility shift assays that TIAR can bind directly to single-stranded, thymidine-rich ODNs but not to double-stranded ODNs containing the same sequence [13].
  • Taken together, these results indicate that in addition to transcriptional regulation, another mechanism by which apigenin prevents COX-2 expression is through mediating TIAR suppression of translation [12].
  • Although RRM 3 (of either TIA-1 or TIAR) does not interact with the uridylate-rich sequences selected by the full-length proteins, it is a bona fide RNA binding domain capable of affinity-precipitating a population of cellular RNAs ranging in size from 0.5 to 5 kilobases [14].
  • On the other hand, TCBP did not affect expression from the PF4 promoter in which the T-cluster and the T-rich region had been removed [15].

Physical interactions of TIAL1

  • Pub1p, an ELAV-like yeast RNA-binding protein with homology to T-cell internal antigen 1 (TIA-1)/TIA-1-related protein (TIAR), is an important modulator of the decay of two known classes of mRNA [16].
  • In RNA binding studies TIAR displayed high affinity binding to the human iNOS 3'-UTR sequence [17].
  • Gel mobility shift analysis demonstrated that recombinant TCBP specifically bound to the T-cluster and the proximal T-rich region of the PF4 promoter [15].

Regulatory relationships of TIAL1

  • Using in vitro splicing assays, we have shown that TIA-1 is directly involved in activating the 5' splice sites of the TIAR alternative exons [18].
  • However, overexpression of TIAR in human DLD-1 colon carcinoma cells resulted in enhanced cytokine-induced iNOS expression [17].

Other interactions of TIAL1

  • Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of the functional roles of these proteins during mammalian development [19].
  • Immunoprecipitation analysis indicated that HuR, KSRP and TIAR bound to one or more loci in the 3'UTR [20].
  • From these six genes, NFE2L2 and TIAL1 were selected as genes associated with poor prognosis by means of a validation study with another set of 56 ER-positive breast cancers [21].
  • Truncation of TIAR indicated that the high affinity DNA-binding site overlaps with the RNA-binding site involving RNA recognition motif 2 (RRM2) [13].
  • In addition to the 3'-untranslated region of the matrix metalloproteinases-13 (MMP13) gene, the differential expression of an alternatively spliced transcript of the RNA-binding protein TIAR in human cell cultures is also critical for this post-transcriptional regulation [22].

Analytical, diagnostic and therapeutic context of TIAL1

  • TIAR moves from the nucleus to the cytoplasm within 30 min of Fas ligation [9].
  • Although immunoblotting analysis of post-nuclear supernatants revealed TIA-1 protein to be restricted to CTLs, PCR analysis revealed the expression of TIA-1 and TIAR mRNA transcripts in a wide variety of cell types [10].
  • Duplication of this AU-rich sequence alone within the le RNA confers TIAR binding on this le* RNA and a non-cytopathic phenotype to these rSeV in cell culture [1].
  • This article presents a case and rationale for implant-supported par tial overdentures [23].
  • Positive end expiratory pressure did not effect end tial CO2 during "controlled breathing" but caused an increase during "spontaneous breathing" when fresh gas flow was less than 3 times the minute volume [24].


  1. Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis. Iseni, F., Garcin, D., Nishio, M., Kedersha, N., Anderson, P., Kolakofsky, D. EMBO J. (2002) [Pubmed]
  2. Cell proteins TIA-1 and TIAR interact with the 3' stem-loop of the West Nile virus complementary minus-strand RNA and facilitate virus replication. Li, W., Li, Y., Kedersha, N., Anderson, P., Emara, M., Swiderek, K.M., Moreno, G.T., Brinton, M.A. J. Virol. (2002) [Pubmed]
  3. Herpes simplex virus 1 induces cytoplasmic accumulation of TIA-1/TIAR and both synthesis and cytoplasmic accumulation of tristetraprolin, two cellular proteins that bind and destabilize AU-rich RNAs. Esclatine, A., Taddeo, B., Roizman, B. J. Virol. (2004) [Pubmed]
  4. Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury. Jin, K., Li, W., Nagayama, T., He, X., Sinor, A.D., Chang, J., Mao, X., Graham, S.H., Simon, R.P., Greenberg, D.A. J. Neurosci. Res. (2000) [Pubmed]
  5. Increased expression of the TIAR protein in the hippocampus of Alzheimer patients. Oleana, V.H., Salehi, A., Swaab, D.F. Neuroreport (1998) [Pubmed]
  6. Investigating the role of desorption on the bioavailability of sediment-associated 3,4,3',4'-tetrachlorobiphenyl in benthic invertebrates. Leppänen, M.T., Landrum, P.F., Kukkonen, J.V., Greenberg, M.S., Burton, G.A., Robinson, S.D., Gossiaux, D.C. Environ. Toxicol. Chem. (2003) [Pubmed]
  7. On Again, off Again: The SRC-3 Transcriptional Coactivator Moonlights as a Translational Corepressor. Anderson, P., Kedersha, N. Mol. Cell (2007) [Pubmed]
  8. Posttranscriptional derepression of GADD45alpha by genotoxic stress. Lal, A., Abdelmohsen, K., Pullmann, R., Kawai, T., Galban, S., Yang, X., Brewer, G., Gorospe, M. Mol. Cell (2006) [Pubmed]
  9. The RNA-binding protein TIAR is translocated from the nucleus to the cytoplasm during Fas-mediated apoptotic cell death. Taupin, J.L., Tian, Q., Kedersha, N., Robertson, M., Anderson, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  10. Identification and functional characterization of a TIA-1-related nucleolysin. Kawakami, A., Tian, Q., Duan, X., Streuli, M., Schlossman, S.F., Anderson, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  11. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Kedersha, N., Anderson, P. Biochem. Soc. Trans. (2002) [Pubmed]
  12. Apigenin prevents UVB-induced cyclooxygenase 2 expression: coupled mRNA stabilization and translational inhibition. Tong, X., Van Dross, R.T., Abu-Yousif, A., Morrison, A.R., Pelling, J.C. Mol. Cell. Biol. (2007) [Pubmed]
  13. Novel DNA-binding properties of the RNA-binding protein TIAR. Suswam, E.A., Li, Y.Y., Mahtani, H., King, P.H. Nucleic Acids Res. (2005) [Pubmed]
  14. Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities. Dember, L.M., Kim, N.D., Liu, K.Q., Anderson, P. J. Biol. Chem. (1996) [Pubmed]
  15. An alternative form of nucleolysin binds to a T-cluster DNA in the silencer element of platelet factor 4 gene. Doi, T., Minami, T., Itoh, M., Aburatani, H., Kawabe, Y., Kodama, T., Kondo, N., Satoh, Y., Asayama, T., Imanishi, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  16. Global analysis of Pub1p targets reveals a coordinate control of gene expression through modulation of binding and stability. Duttagupta, R., Tian, B., Wilusz, C.J., Khounh, D.T., Soteropoulos, P., Ouyang, M., Dougherty, J.P., Peltz, S.W. Mol. Cell. Biol. (2005) [Pubmed]
  17. The RNA binding protein TIAR is involved in the regulation of human iNOS expression. Fechir, M., Linker, K., Pautz, A., Hubrich, T., Kleinert, H. Cell. Mol. Biol. (Noisy-le-grand) (2005) [Pubmed]
  18. TIA-1 and TIAR activate splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on their own pre-mRNAs. Le Guiner, C., Lejeune, F., Galiana, D., Kister, L., Breathnach, R., Stévenin, J., Del Gatto-Konczak, F. J. Biol. Chem. (2001) [Pubmed]
  19. Structure, tissue distribution and genomic organization of the murine RRM-type RNA binding proteins TIA-1 and TIAR. Beck, A.R., Medley, Q.G., O'Brien, S., Anderson, P., Streuli, M. Nucleic Acids Res. (1996) [Pubmed]
  20. IL-1beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via the 3' untranslated region: Involvement of divergent RNA-binding factors HuR, KSRP and TIAR. Suswam, E.A., Nabors, L.B., Huang, Y., Yang, X., King, P.H. Int. J. Cancer (2005) [Pubmed]
  21. High expression of two genes selected by iAFLP: a new prognostic factor of estrogen receptor-positive breast cancer. Aritake, N., Tamaki, Y., Masuda, N., Nakano, Y., Monden, T., Noguchi, S., Monden, M. Oncol. Rep. (2004) [Pubmed]
  22. Translational repression of human matrix metalloproteinases-13 by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (TIAR). Yu, Q., Cok, S.J., Zeng, C., Morrison, A.R. J. Biol. Chem. (2003) [Pubmed]
  23. Treatment planning: implant-supported partial overdentures. Chee, W.W. Journal of the California Dental Association. (2005) [Pubmed]
  24. The effect of positive end expiratory pressure on rebreathing and gas dilution in the Ayre's T-piece system--a laboratory study. Dobbinson, T.L., Fawcett, E.R., Bolton, D.P. Anaesthesia and intensive care. (1978) [Pubmed]
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