Tia1 - cytotoxic granule-associated RNA binding protein 1 (house mouse)
Gene
Symbol
Taxonomy
Dates
- Create:2016-09-14
- Modify:2025-02-02
Description
Enables mRNA 3'-UTR AU-rich region binding activity. Involved in negative regulation of translation and regulation of alternative mRNA splicing, via spliceosome. Acts upstream of or within negative regulation of cytokine production. Located in cytoplasmic stress granule and nuclear stress granule. Is expressed in several structures, including alimentary system; brain; metanephros; respiratory system; and sensory organ. Human ortholog(s) of this gene implicated in amyotrophic lateral sclerosis type 26. Orthologous to human TIA1 (TIA1 cytotoxic granule associated RNA binding protein).
- 2310050N03Rik
- TIA-1
- mTIA-1
- cytotoxic granule associated RNA binding protein TIA1
- RNA-binding protein TIA-1
- T-cell-restricted intracellular antigen-1
- nucleolysin TIA-1
- RNA-Binding Protein TIA-1
- T-Cell-Restricted Intracellular Antigen-1
RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences (PMID: 10938105, PMID: 16227602). Binds to U-rich sequences immediately downstream from a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing (PMID: 10938105). Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is optimal if a 5' splice site is adjacent to IAS1 (PMID: 10938105). Activates the use of heterologous 5' splice sites; the activation depends on the intron sequence downstream from the 5' splice site, with a preference for a downstream U-rich sequence (PMID: 10938105). By interacting with SNRPC/U1-C, promotes recruitment and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences, thereby facilitating atypical 5' splice site recognition by U1 snRNP (By similarity). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIAR mRNA (PMID: 11514562). Acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis (By similarity). Binds to the 5' splice site region of FAS intron 5 to promote accumulation of transcripts that include exon 6 at the expense of transcripts in which exon 6 is skipped, thereby leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis (By similarity). Binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2 (By similarity). Also binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby be involved in the regulation of transcription (By similarity). Involved in the repression of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs), including target ARE-bearing mRNAs encoding TNF and PTGS2 (PMID: 10921895, PMID: 16227602). Also participates in the cellular response to environmental stress, by acting downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs), leading to stress-induced translational arrest (By similarity). Formation and recruitment to SGs is regulated by Zn(2+) (PMID: 29298433). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (By similarity).
Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605
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