| Category | Key points (1-2 sentences) | Key evidence citations | Key sources with year and URL |
|---|---|---|---|
| Identity/Domains | UniProt P31483 corresponds to human TIA1/TIA-1, a multifunctional RNA-binding protein with three N-terminal RRMs and a C-terminal glutamine-rich low-complexity/prion-like domain that supports protein-protein interactions and condensate formation. TIA1 shuttles between nucleus and cytoplasm, consistent with roles in splicing and stress responses. | (pqac-00000001, pqac-00000004, pqac-00000017) | Fotouhi et al., 2024, https://doi.org/10.12688/f1000research.133645.2; Alcalde-Rey et al., 2024, https://doi.org/10.3390/cells13231961; Wang et al., 2014, https://doi.org/10.1093/nar/gku193 |
| RNA binding specificity | TIA1 preferentially recognizes uridine-rich/pyrimidine-rich RNA, including 3' U-rich elements and intronic U-rich motifs downstream of 5' splice sites. RRM2 is the principal sequence-specific RNA-binding domain, RRM3 enhances/cooperates with RRM2, and RRM1 contributes little intrinsic RNA affinity. | (pqac-00000001, pqac-00000006, pqac-00000016, pqac-00000018) | Fotouhi et al., 2024, https://doi.org/10.12688/f1000research.133645.2; Ramos-Velasco et al., 2024, https://doi.org/10.3390/biology13030195; Wang et al., 2014, https://doi.org/10.1093/nar/gku193; Wang et al., 2010, https://doi.org/10.1371/journal.pbio.1000530 |
| Splicing mechanism | TIA1 binds U-rich motifs typically 10-28 nt downstream of 5' splice sites and promotes exon inclusion by facilitating U1 snRNP/U1-C recognition of weak 5' splice sites, exemplified by FAS exon 6 regulation. Structural studies show RRMs are modular when free but form a compact cooperative RNA-bound complex. | (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019) | Wang et al., 2014, https://doi.org/10.1093/nar/gku193; Wang et al., 2010, https://doi.org/10.1371/journal.pbio.1000530; Bauer et al., 2012, https://doi.org/10.1016/j.jmb.2011.11.040 |
| Stress granules/LLPS | The C-terminal low-complexity/prion-like domain drives liquid-liquid phase separation and stress granule (SG) assembly, linking eIF2α-dependent translational arrest to cytoplasmic mRNA triage. TIA1 is a canonical SG component, and altered SG assembly/disassembly is a major mechanistic theme in TIA1-linked pathology. | (pqac-00000004, pqac-00000006, pqac-00000003, pqac-00000005) | Alcalde-Rey et al., 2024, https://doi.org/10.3390/cells13231961; Ramos-Velasco et al., 2024, https://doi.org/10.3390/biology13030195; Fuentes-Jiménez et al., 2023, https://doi.org/10.3389/fcell.2023.1265104 |
| Immune-cell functions | In immune cells, TIA1/TIAL1 help enforce T-cell quiescence and regulate GC B-cell survival and selection. A 2023 study identified 1,487 high-confidence TIA1/TIAL1 target genes in GC B cells and showed direct control of Mcl1 translation, with knockout causing increased apoptosis and defective high-affinity antibody responses. | (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000013) | Osma-Garcia et al., 2023, https://doi.org/10.1038/s41423-023-01063-4; Osma-Garcia et al., 2024, https://doi.org/10.1101/2024.09.03.608755; Ramos-Velasco et al., 2024, https://doi.org/10.3390/biology13030195 |
| Disease links/variants | TIA1 variants are implicated in neurodegeneration (especially ALS/FTD spectrum) and Welander distal myopathy; disease-associated mutations in the low-complexity domain can delay SG disassembly or perturb phase behavior. The founder p.E384K variant is the best-established myopathy-linked example discussed in recent literature. | (pqac-00000001, pqac-00000004, pqac-00000003) | Fotouhi et al., 2024, https://doi.org/10.12688/f1000research.133645.2; Alcalde-Rey et al., 2024, https://doi.org/10.3390/cells13231961; Fuentes-Jiménez et al., 2023, https://doi.org/10.3389/fcell.2023.1265104 |
| Quantitative stats | Reported quantitative data include ~630 nM TIA1 and ~3.8×10^5 copies/cell in HEK-293T cells, plus low RNA-protein correlation in T cells (r² = 0.4). Structural work further shows RRM2,3 binds FAS-derived/U-rich RNA with nanomolar affinity, and RNA binding compacts the protein-RNA complex; GC B-cell iCLIP identified 1,487 high-confidence targets and 1,162 DE genes in dark-zone knockout cells. | (pqac-00000012, pqac-00000010, pqac-00000016, pqac-00000020, pqac-00000008) | Ramos-Velasco et al., 2024, https://doi.org/10.3390/biology13030195; Osma-Garcia et al., 2024, https://doi.org/10.1101/2024.09.03.608755; Wang et al., 2014, https://doi.org/10.1093/nar/gku193; Osma-Garcia et al., 2023, https://doi.org/10.1038/s41423-023-01063-4 |
| Tools/applications | Practical uses include TIA1 immunohistochemistry as a biomarker of cytotoxic CD8+ tumor-infiltrating lymphocytes/prognosis in some cancers, and a 2024 validated antibody-selection resource for Western blot, immunoprecipitation, and immunofluorescence. Common experimental tools for TIA1 functional annotation include iCLIP/irCLIP, luciferase reporters, flow cytometry, ribosome-block assays, and stress-granule imaging. | (pqac-00000013, pqac-00000001, pqac-00000008, pqac-00000011) | Ramos-Velasco et al., 2024, https://doi.org/10.3390/biology13030195; Fotouhi et al., 2024, https://doi.org/10.12688/f1000research.133645.2; Osma-Garcia et al., 2023, https://doi.org/10.1038/s41423-023-01063-4 |


*Table: This table summarizes the core functional annotation of human TIA1 (UniProt P31483), covering identity, RNA-binding and splicing mechanisms, stress granules, immune functions, disease associations, quantitative findings, and practical research applications. It is useful as a compact evidence map for the full report.*