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FLASH GENE
Symbol TIA1 contributors: mct - updated : 29-08-2023
HGNC name TIA1 cytotoxic granule-associated RNA binding protein
HGNC id 11802
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three N-terminal RNA recognition motifs (RRMs), and any one RRM in combination with a Q domain is necessary and sufficient for TIA1-associated regulation of SMN2 exon 7 splicing
  • a prion-related domain
  • a C-terminal glutamine-rich (Q-rich) domain
    • isoforms Precursor p40-TIA1, precursor of a 15 kDa (p15-TIA-1) protein
    HOMOLOGY
    interspecies homolog to murine Tia1
    homolog to rattus LOC312510
    intraspecies paralog to TIAL1
    Homologene
    FAMILY
  • U-rich element mRNA-binding protein family
    • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleoplasm
    text
  • also colocalizing with POLR in stress granules, initiated by the phosphorylayion of EIF2A
  • subcellular nucleo-cytoplasmic localization
    • basic FUNCTION
  • cytotoxic granule associated RNA binding protein
  • regulator of alternative pre-mRNA splicing
  • may be involved in induction of apoptosis
  • may have dual role in shuttling between DNA and RNA ligands to co-regulate COL2A1 expression at the level of transcription and pre-mRNA alternative splicing
  • major granule associated species
  • translational silencer of COX2, selectively regulating the expression of TNF
  • nucleolytic activity against cytotoxic lymphocyte target cells
  • acting as a post-transcriptional silencer, and suppressing the production of the TNF-alpha protein
  • TIA1, and TIAL1 are mRNA-binding proteins that can aggregate within granules under specific stress conditions
  • its expression counteracts the inhibitory effect of polypyrimidine tract binding protein, a ubiquitously expressed factor recently implicated in regulation of SMN exon 7 splicing
  • role of TIA1 phosphorylation in autophagy
  • TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis
  • essential contributions of the TIA1 and TIAL1 to the fidelity of mRNA maturation, translation, and RNA-stress-sensing pathways in human cells
  • is an important regulator of the innate immune response in the periphery, dampening cytotoxic inflammation and apoptosis during cellular stress
  • likely TIA1 dampens the immune response in the central nervous system during chronic stress
  • RNA-binding protein that can regulate splicing, stability, or translation of target mRNAs, and play critical roles in stress response and neurodevelopment
  • translation repression is a key process targeted by TIA1 binding which implicate TIA1 function in neuronal differentiation
  • TIA1 appears to control the expression of both pro- and anti-tumorigenic factors in hepatic cancer cells
  • in pro-B cells, the RNA-binding proteins T cell intracellular antigen 1 (TIA1) and TIA1-like protein (TIAL1) act redundantly to enable developmental progression
  • importance of tight regulation of RNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs that control DNA damage sensing and repair during B cell development
  • TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific germinal centers (GCs) B cells
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
  • binding
  • poly(A) binding
    • small molecule
    protein
  • ARE element of TNF
  • binding to FASTK
  • interacts with a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of exon 2
  • interacting with RPS6KA3 (the RPS6KA3 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA1)
  • KHDRBS1 complexed with T-cell intracellular antigen-1 (TIA1), a core SG component, and that the complex formation was correlated with stress granules (SG) recruitment
  • regulate SMN exon 7 splicing by binding to intron 7 sequences away from the 5prime ss
  • TIA1 and TIAL1 proteins are intron-associated positive regulators of SMN2 exon 7 splicing
  • ANXA7 is an interaction protein of TIA1
    • cell & other
    REGULATION
    Other regulated by TARDBP (TARDBP contributes to both the assembly and maintenance of stress granules (SGs)in response to oxidative stress and differentially regulates key SGs components, including TIA1 and G3BP1)
    rapid and severe hypoxia caused co-aggregation of TIAL1/TIA1 and these proteins suppressed HIF1A expression
    ASSOCIATED DISORDERS
    corresponding disease(s) ALS26 , WDM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    expressed in synovium of patients with rheumatoid arthritis
    constitutional     --over  
    in the thyroid tissues in patients with Graves disease
    tumoral     --low  
    in hepatocellular carcinoma (HCC)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • TIA1 is a biomarker in HCC
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    TIA1 is a therapeutic target in HCC
    ANIMAL & CELL MODELS