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; OMA:TIA1 - orthologs
Gene location (Mouse) Chr. Chromosome 6 (mouse)[1] Band 6|6 D1 Start 86,381,201 bp[1] End 86,410,387 bp[1]
Gene ontology Molecular function nucleic acid binding protein binding poly(A) binding RNA binding mRNA 3'-UTR AU-rich region binding Cellular component cytoplasm cytoplasmic stress granule nuclear stress granule nucleus nucleoplasm cytosol ribonucleoprotein complex Biological 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: 86.38 – 86.41 Mb PubMed search [2] [3]
Wikidata
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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]

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.^[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.

See also

• Stress granule
• T-cell large granular lymphocyte leukemia