Affinage

TIAL1

Nucleolysin TIAR · UniProt Q01085

Length
375 aa
Mass
41.6 kDa
Annotated
2026-04-28
65 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIAL1 (TIAR) is a multi-functional RNA-binding protein containing three RNA recognition motifs (RRMs) that operates as a central post-transcriptional regulator of mRNA splicing, translation, and stress-responsive mRNA triage. RRM2 is the primary high-affinity binding domain for U-rich and C-rich RNA as well as T-rich ssDNA, while RRM1 enhances affinity cooperatively and RRM3 mediates nuclear export; TIAR continuously shuttles between nucleus and cytoplasm via Ran-GTP-dependent import through RRM2 and CRM1-independent export through RRM3 (PMID:8576255, PMID:16278295, PMID:23603827). TIAR promotes inclusion of alternative exons flanked by U-rich intronic sequences downstream of weak 5′ splice sites genome-wide—including autoregulatory splicing of its own pre-mRNA—and controls expression of DNA damage sensors in pro-B cells (PMID:11514562, PMID:18456862, PMID:36543128); it represses translation of diverse mRNAs (5′TOP mRNAs, MYC, BRCA1, HIF-1α, translation factors, Insig2/ApoB) by binding 3′-UTR AU-rich or C-rich elements, and assembles into cytoplasmic stress granules downstream of eIF2α phosphorylation to sequester untranslated mRNAs during stress (PMID:10613902, PMID:16537914, PMID:17486099, PMID:21979918, PMID:37296170). Beyond RNA-dependent functions, TIAR sequesters CDK1 in nuclear G2/M transition granules to restrain mitotic entry, facilitates flavivirus genome amplification by binding minus-strand RNA, and suppresses Hippo signaling through an RNA-binding-independent interaction with SAV1 (PMID:30538118, PMID:18768985, PMID:42032365).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Establishing that TIAR is a predominantly nuclear protein that undergoes regulated nuclear-to-cytoplasmic redistribution during apoptosis resolved where and when TIAR acts, linking its subcellular dynamics to cell-death signaling.

    Evidence Immunofluorescence and subcellular fractionation during Fas-ligation time-course in hematopoietic cells

    PMID:7533298

    Open questions at the time
    • Mechanism of nuclear export during apoptosis not defined
    • Whether redistribution is required for apoptosis execution not tested
  2. 1996 High

    Mapping high-affinity U-rich RNA binding to RRM2 (with cooperative contributions from RRM1 and RRM3) defined the molecular basis for TIAR target recognition, enabling all subsequent studies of its RNA-binding specificity.

    Evidence SELEX, filter-binding, and affinity precipitation with individual recombinant RRM domains

    PMID:8576255

    Open questions at the time
    • Structural basis of RRM2 selectivity not yet resolved
    • In vivo target spectrum not addressed
  3. 1998 High

    Demonstrating that TIAR-knockout mice lose primordial germ cells and that TIAR-deficient ES cells require exogenous LIF for proliferation established TIAR as essential for cell survival and germ cell development.

    Evidence Gene-targeted knockout mice with embryonic staging; ES cell proliferation assay in methylcellulose

    PMID:9482885

    Open questions at the time
    • Specific mRNA targets mediating PGC survival not identified
    • Redundancy with TIA-1 in vivo not fully dissected
  4. 1999 High

    Placing TIAR downstream of eIF2α phosphorylation in stress granule assembly provided the first mechanistic framework for how cells sequester untranslated mRNAs during stress, and showing that TIAR also binds TNF-α ARE linked it to cytokine translational control.

    Evidence Phosphomimetic/non-phosphorylatable eIF2α mutants with SG imaging; UV cross-linking and gel-shift with TNF-α ARE

    PMID:10613902 PMID:9890998

    Open questions at the time
    • How TIAR nucleates SG condensation mechanistically was unknown
    • Relative contributions of TIA-1 vs TIAR to SG nucleation not separated
  5. 2001 High

    Showing that TIAR activates inclusion of alternative exons with weak 5′ splice sites by binding downstream U-rich intronic sequences—including autoregulatory exons in its own pre-mRNA—established TIAR as a sequence-specific splicing activator.

    Evidence In vitro splicing reconstitution with U-rich element deletions; in vivo overexpression with minigene reporters

    PMID:11514562

    Open questions at the time
    • How TIAR promotes U1 snRNP recruitment mechanistically was unclear
    • Genome-wide scope of splicing regulation not yet measured
  6. 2002 High

    Identification of TIAR as a high-affinity binding partner of the WNV minus-strand 3′ stem-loop, with reduced viral growth in TIAR-KO cells, revealed an unexpected role for a host RNA-binding protein in flavivirus genome amplification.

    Evidence RNA affinity purification, peptide sequencing, Kd measurement, TIAR-KO cell viral growth and rescue

    PMID:12414941

    Open questions at the time
    • Precise mechanism by which TIAR facilitates minus-to-plus strand synthesis not defined
    • Applicability to other flaviviruses not yet tested
  7. 2005 High

    Defining that TIAR continuously shuttles between nucleus and cytoplasm—with RRM2 driving Ran-GTP-dependent nuclear import and RRM3 mediating CRM1-independent export—explained how TIAR can function in both nuclear splicing and cytoplasmic translational control, and revealing high-affinity ssDNA binding expanded the repertoire of potential TIAR substrates.

    Evidence GFP-domain mutants with Ran depletion and leptomycin B treatment; UV cross-linking and EMSA with ssDNA Kd measurements

    PMID:16091628 PMID:16278295

    Open questions at the time
    • Physiological relevance of DNA binding in vivo not demonstrated
    • Export receptor/adaptor identity unknown
  8. 2006 High

    Demonstrating that TIAR represses translation of mRNAs encoding translation factors and c-Myc via 3′-UTR binding, and that FASTK phosphorylation of TIA-1/TIAR enhances U1 snRNP recruitment for Fas exon 6 splicing, revealed dual regulatory outputs (translational repression and splicing activation) modulated by upstream kinase signaling.

    Evidence RNP-IP with polysome profiling and siRNA knockdown; FASTK phosphorylation assays with minigene splicing reporters

    PMID:16537914 PMID:17135269

    Open questions at the time
    • Full kinase network regulating TIAR not mapped
    • Whether FASTK also regulates TIAR's translational function not tested
  9. 2007 High

    Discovery that TIAR binds a C-rich stem-loop motif in addition to U-rich sequences, and that AUF1 and TIAR competitively regulate MYC mRNA translation, broadened the RNA target code and revealed combinatorial control of specific transcripts.

    Evidence RNP-IP/microarray with SPR validation for C-rich motif; competitive ARE-binding and polysome profiling for MYC regulation

    PMID:17486099 PMID:17682065

    Open questions at the time
    • Structural basis for C-rich motif recognition not determined
    • How the AUF1-TIAR balance is regulated upstream not known
  10. 2008 High

    Genome-wide splicing analysis confirmed that TIA1/TIAL1 control ~88% of alternative exons flanked by downstream U-rich motifs, and infectious-clone mutagenesis mapped the precise TIAR-binding sites on WNV minus-strand RNA required for viral genome amplification.

    Evidence Splicing-sensitive microarray after TIA1/TIAL1 knockdown; WNV infectious clone mutagenesis with binding and replication assays

    PMID:18456862 PMID:18768985

    Open questions at the time
    • How TIAR binding promotes asymmetric replication mechanistically not resolved
    • Redundancy between TIA-1 and TIAR in splicing regulation not fully dissected
  11. 2011 High

    Showing that TIAR assembles onto 5′TOP mRNAs during amino acid starvation downstream of GCN2 activation and mTOR inactivation placed TIAR in a nutrient-sensing translational repression pathway, and biophysical characterization revealed that TIAR RRM1-2 adopts an elongated conformation distinct from HuR, explaining differential RNA/DNA binding modes.

    Evidence Polysome profiling with RIP under amino acid starvation, GCN2/mTOR inhibition; SPR and SAXS structural analysis

    PMID:21233170 PMID:21979918

    Open questions at the time
    • How TIAR recognizes 5′TOP sequences specifically vs general U-rich elements not clarified
    • Whether elongated conformation is altered by post-translational modifications unknown
  12. 2013 High

    NMR mapping of the RNA-contacting residues in RRM2 plus its C-terminal six-amino-acid linker provided the first atomic-level view of TIAR's primary RNA-binding surface.

    Evidence NMR spectroscopy combined with SPR binding of domain-specific constructs

    PMID:23603827

    Open questions at the time
    • No high-resolution co-crystal structure of RRM2-RNA complex
    • How RRM1 and RRM3 cooperate structurally with RRM2 not resolved
  13. 2018 High

    Discovery that TIAR accumulates in nuclear G2/M transition granules that sequester CDK1, thereby restraining mitotic entry under replication stress, revealed a cell-cycle checkpoint function distinct from its canonical mRNA regulatory roles.

    Evidence Immunofluorescence time-course, TIAR siRNA with genetic epistasis (Cdc25B co-depletion, CDK1 inhibition), CDK1 activity assays

    PMID:30538118

    Open questions at the time
    • Whether CDK1 sequestration requires TIAR RNA binding or phase separation not determined
    • Upstream signal targeting TIAR to GMGs not identified
  14. 2019 High

    Demonstration that the C. elegans ortholog TIAR-2 undergoes phosphorylation-regulated liquid-liquid phase separation via its prion-like domain to inhibit axon regeneration provided in vivo evidence that TIAR granule formation is a regulated biophysical process with specific biological consequences.

    Evidence In vitro phase separation assays, PrLD deletion/tyrosine mutants, phosphomutants, axon regeneration assays in C. elegans

    PMID:31378567

    Open questions at the time
    • Whether mammalian TIAR PrLD undergoes analogous regulated phase separation not shown
    • Kinase responsible for TIAR-2 phosphorylation not identified
  15. 2022 High

    In vivo CLIP-seq in pro-B cells confirmed that TIA1/TIAL1 bind 5′ splice sites genome-wide for exon definition and showed that their loss deregulates DNA damage sensors (Chek2, Rif1), leading to exacerbated DNA damage and cell death, connecting TIAR's splicing function to genomic integrity.

    Evidence Conditional double knockout in pro-B cells with CLIP-seq and RNA-seq; DNA damage marker analysis

    PMID:36543128

    Open questions at the time
    • Whether TIAR has splicing-independent roles in DNA damage response not tested
    • Cell-type specificity of the DNA damage phenotype not explored
  16. 2023 High

    In vivo PAR-CLIP in mouse liver identified Insig2 and ApoB as direct TIAR targets whose translational regulation controls cholesterol homeostasis, while studies in germinal center B cells showed TIAR controls translational identity including MCL1 pro-survival expression, demonstrating tissue-specific translational programs governed by TIAR.

    Evidence viP-CLIP in liver with Tial1 mutant mice and cholesterol phenotyping; conditional B-cell KO with polysome profiling

    PMID:37296170 PMID:37474714

    Open questions at the time
    • Full tissue-specific target repertoire remains to be catalogued
    • How TIAR selects different target sets in different tissues not mechanistically resolved
  17. 2025 Medium

    Identification of an RNA-binding-independent interaction between TIAR and SAV1 that disrupts the MST1-SAV1 complex to suppress Hippo signaling expanded TIAR's functional repertoire beyond nucleic acid regulation, and characterization of the TIAR 5′ UTR feature conferring resistance to SARS-CoV-2 Nsp1-mediated translational shutoff revealed a mechanism for TIAR autoprotection during viral infection.

    Evidence Co-IP with RNA-binding-deficient mutants and YAP activity reporters; systematic 5′ UTR mutagenesis in reporter shutoff assays

    PMID:41407513 PMID:42032365

    Open questions at the time
    • Whether Hippo pathway regulation occurs in vivo in tissues not shown
    • Whether Nsp1 resistance confers a selective advantage during SARS-CoV-2 infection in physiological context not tested
    • Single-lab findings for both discoveries

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the structural basis of TIAR phase separation and granule nucleation in mammalian cells; how upstream signaling pathways (kinases, PTMs) coordinate TIAR's partitioning among splicing, translational repression, stress granule, and Hippo pathway functions; the physiological role of TIAR's high-affinity ssDNA binding; and the tissue-specific logic by which TIAR selects different mRNA target repertoires.
  • No high-resolution structure of full-length TIAR or its phase-separated state
  • Kinase/phosphatase network controlling TIAR localization and function largely unmapped
  • In vivo relevance of ssDNA binding untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 6 GO:0005634 nucleus 3
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-8953854 Metabolism of RNA 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1430728 Metabolism 1 R-HSA-162582 Signal Transduction 1 R-HSA-1640170 Cell Cycle 1
Partners
AUF1CDK1FASTKHMGB1HNRNPUHURSAV1TIA1
Complex memberships
G2/M transition granulesstress granules

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Assembly of TIA-1/TIAR-positive stress granules (SGs) is initiated downstream of eIF-2α phosphorylation; a phosphomimetic eIF-2α mutant (S51D) induces SG assembly, a non-phosphorylatable mutant (S51A) prevents it, and a TIAR mutant lacking RNA-binding domains acts as a transdominant inhibitor of SG formation, placing TIAR downstream of eIF-2α in the pathway that sequesters untranslated mRNAs. Phosphomimetic/non-phosphorylatable eIF-2α mutants, transdominant-negative TIAR mutant overexpression, fluorescence microscopy of SG assembly The Journal of cell biology High 10613902
1996 RRM2 of both TIA-1 and TIAR is the domain responsible for high-affinity, specific binding to uridylate-rich RNA sequences; RRM1 does not bind cellular RNA in affinity-precipitation assays, while RRM3 binds a broad population of cellular RNAs; affinity increases when RRM2 is expressed together with RRM1 and RRM3. In vitro SELEX, filter-binding assays with individual recombinant RRM domains, affinity precipitation The Journal of biological chemistry High 8576255
1995 TIAR is concentrated in the nucleus of hematopoietic and non-hematopoietic cells and translocates from the nucleus to the cytoplasm within 30 min of Fas ligation, preceding the onset of DNA fragmentation during Fas-mediated apoptosis; this redistribution is not observed during mitogenic activation. Immunofluorescence microscopy, subcellular fractionation, Fas ligation time-course Proceedings of the National Academy of Sciences of the United States of America High 7533298
1999 TIAR binds directly to the AU-rich element (ARE) of TNF-α mRNA (requiring clustered AUUUA pentamers) in the cytoplasm of macrophages, implicating it in translational repression of TNF-α. RNA-protein complex identification by competition gel mobility shift and UV cross-linking, cytoplasmic localization by fractionation The Journal of biological chemistry High 9890998
1998 TIAR is essential for primordial germ cell (PGC) survival and development; TIAR-knockout mice show severely reduced PGC numbers by E11.5 and complete absence by E13.5, and TIAR-deficient ES cells fail to proliferate without exogenous LIF, consistent with a role for TIAR in regulating a survival/proliferation factor. Knockout mouse (gene targeting), embryo staging, methylcellulose ES cell proliferation assay Proceedings of the National Academy of Sciences of the United States of America High 9482885
2001 TIAR (like TIA-1) activates splicing of alternative exons with weak 5' splice sites that are followed by U-rich intronic sequences on the TIA-1 and TIAR pre-mRNAs themselves, demonstrating autoregulatory splicing; in vitro splicing assays showed direct activation requires a downstream U-rich stretch of ≥10 residues. Overexpression in cells, in vitro splicing assays, deletion of U-rich stretches, cryptic splice-site analysis The Journal of biological chemistry High 11514562
2002 TIAR (p42) was purified by RNA affinity chromatography and identified by peptide sequencing as a specific binding partner of the West Nile virus 3'-terminal minus-strand stem-loop (WNV 3'(-)SL) RNA; binding maps to RRM2 with Kd ~1.5×10⁻⁸ M (10-fold tighter than TIA-1 RRM2); WNV growth is less efficient in TIAR-knockout cells and is partially rescued by TIAR reconstitution. RNA affinity column purification, peptide sequencing, competition gel-shift assays with recombinant proteins, TIAR knockout cell lines, viral reconstitution Journal of virology High 12414941
2006 TIAR selectively binds the 3'-UTRs of mRNAs encoding translation factors (eIF4A, eIF4E, eEF1B) and c-Myc, potently suppressing their translation particularly in response to UVC irradiation; silencing TIAR significantly relieves UVC-induced global translational arrest. RNP immunoprecipitation, polysome profiling, TIAR siRNA knockdown, reporter assays Molecular and cellular biology High 16537914
2007 AUF1 and TIAR competitively bind the ARE of MYC mRNA to regulate its translation: MYC translation and cell proliferation are proportional to AUF1 abundance and inversely proportional to TIAR abundance; altering one protein's mRNA association reciprocally affects the other's; genetic experiments place both in a MYC-dependent proliferation pathway. ARE-binding competition assays, polysome profiling, siRNA knockdown, genetic epistasis (MYC-dependent pathway) Nature structural & molecular biology High 17486099
2011 Upon amino acid starvation, TIAR assembles onto the 5' end of 5'TOP mRNAs and arrests their translation at the initiation step, causing polysome release and accumulation in stress granules; this requires GCN2 kinase activation and mTOR inactivation. Polysome profiling, RIP, siRNA knockdown, stress granule imaging, pharmacological inhibition of GCN2 and mTOR Genes & development High 21979918
2008 Simultaneous knockdown of TIA1 and TIAL1 causes increased skipping of 88% of alternatively spliced exons flanked by U-rich intronic motifs downstream of 5' splice sites, but does not affect exons lacking such motifs, demonstrating a genome-wide role for TIAL1 in promoting exon inclusion via U-rich intronic elements. siRNA knockdown of TIA1/TIAL1, splicing-sensitive microarrays, RT-PCR validation, U-rich motif enrichment analysis Genome research High 18456862
2005 TIAR continuously shuttles between nucleus and cytoplasm in a transcription-dependent manner; RRM2 and the first half of the auxiliary region drive nuclear accumulation, while RRM3 mediates nuclear export; nuclear import is Ran-GTP-dependent, whereas export is Ran-GTP- and CRM1-independent; both RRMs function through their RNA-binding capacity. GFP-tagged deletion/point mutants, Ran-GTP depletion, CRM1 inhibition (leptomycin B), live-cell imaging, FRAP-like shuttling assays Journal of cell science High 16278295
2006 Fas-activated serine/threonine kinase (FAST K) phosphorylates TIA-1/TIAR and thereby enhances Fas exon 6 inclusion (pro-apoptotic isoform); depletion of FAST K causes exon 6 skipping, overexpression promotes inclusion, and this effect requires both TIA-1/TIAR and a U-rich intronic enhancer downstream of exon 6; in vitro, FAST K phosphorylation of TIA-1 enhances U1 snRNP recruitment without increasing pre-mRNA binding. FAST K depletion/overexpression, TIA-1/TIAR siRNA, minigene splicing reporters with U-rich enhancer mutations, in vitro phosphorylation and U1 snRNP recruitment assays The Journal of biological chemistry High 17135269
2003 TIAR binds a U-tract sequence downstream of a pseudo 5' splice site in the calcitonin/CGRP intron enhancer and promotes inclusion of the upstream alternative 3'-terminal exon; this binding depends on U1 and U6 snRNA interactions with the pseudo 5' splice site, and TIAR binding in turn promotes U6 snRNA binding, revealing a synergistic relationship. RNA affinity pull-down, EMSA, overexpression of dominant-negative TIAR, in vivo splicing reporters, snRNA binding assays Molecular and cellular biology High 12917321
2007 TIAR associates with subsets of mRNAs bearing a cytosine-rich (~28-32 nt) stem-loop motif in addition to U-rich sequences; in vitro SPR confirmed TIAR (RRM1-2 and RRM1-3) binding to this C-rich motif; insertion of the motif into a reporter strongly suppressed translation; after UVC stress, target mRNAs dissociate from TIAR and encoded proteins increase in a TIAR-dependent manner. RNP immunoprecipitation + microarray, surface plasmon resonance, reporter translational assays, UVC stress dissociation Molecular and cellular biology High 17682065
2005 TIAR binds single-stranded, thymidine/uridine-rich DNA with ~6-fold higher affinity than RNA (Kd ~1.6×10⁻⁹ M vs 9.4×10⁻⁹ M for RNA); the high-affinity DNA-binding site maps to RRM2 (overlapping the RNA-binding site); RRM1 alone also binds DNA; active transcription through the binding site can displace TIAR from ssDNA. UV cross-linking, EMSA, TIAR domain truncations, filter-binding affinity measurements Nucleic acids research High 16091628
2011 TIAR binds both U-rich and AU-rich RNA with nanomolar affinity (higher affinity for U-rich RNA due to faster association); TIAR can also bind deoxy-oligonucleotides with nanomolar affinity whereas HuR affinity for DNA is micromolar; SAXS of TIAR RRM1-2 in complex with RNA shows a flexible, elongated shape distinct from the compact structure of Hu proteins, indicating a different binding mode. Surface plasmon resonance (SPR), SAXS, comparative binding studies with U-rich RNA and DNA Nucleic acids research High 21233170
2013 RRM2 together with its C-terminal six-amino-acid linker extension is the major high-affinity (nM) binding domain for both U-rich RNA and T-rich DNA; RRM1 alone preferentially binds DNA over RNA; NMR spectroscopy identified the specific residues in RRM2+extension involved in RNA contact. SPR, NMR spectroscopy, domain-specific binding assays RNA biology High 23603827
2003 HuR, TIA-1, TIAR, and hnRNP U form a multimeric protein complex on the first 60 nucleotides of the COX-2 mRNA 3'-UTR (containing AUUUA repeats); this complex represses expression, and IL-1β stimulation increases cytosolic HuR binding and COX-2 mRNA levels. EMSA, immunoprecipitation of complex members, reporter gene assay with 60-nt 3'-UTR insert The Journal of biological chemistry Medium 12855701
2002 TIAR binds the AU-rich sequence (5'-UUUUAAAUUUU) in Sendai virus trailer RNA; sequestration of TIAR by this viral RNA has an anti-apoptotic effect; transgenic overexpression of TIAR during SeV infection promotes apoptosis and reverses the anti-apoptotic effect of trailer RNA expression. In vitro binding assays, transgenic TIAR overexpression, apoptosis assays in mixed infections The EMBO journal Medium 12356730
2007 In West Nile virus- and dengue virus-infected cells, TIAR and TIA-1 co-localize with viral replication complex components (dsRNA, NS3) in perinuclear regions; TIAR relocates coincident with peak RNA synthesis, and this interaction suppresses stress granule formation and progressively reduces processing body numbers. Immunofluorescence co-localization, kinetic analysis of TIAR redistribution vs. RNA synthesis Proceedings of the National Academy of Sciences of the United States of America Medium 17502609
2008 TIA-1/TIAR binding sites on the WNV 3'(-)SL RNA were mapped to short AU sequences (UAAUU) in two internal stem-loop loops; mutations abolishing TIAR/TIA-1 binding in infectious clones proportionally reduce viral genomic RNA amplification (not translation), with lethal mutations reverting in vivo, indicating these proteins facilitate asymmetric genome amplification from the minus-strand template. Infectious clone mutagenesis, in vitro binding assays, plaque assays, intracellular RNA quantification Journal of virology High 18768985
2002 An alternatively spliced form of TIAR (containing a 17-amino-acid insert) is expressed in human but not rat cells and is required for species-dependent translational repression of HMMP13 mRNA; transient expression of the insert reverses silencing in human cells, and co-transfection of this isoform suppresses HMMP13 protein expression in Rat2 cells. Reporter assays, transient expression of TIAR isoform and insert peptide, species comparison The Journal of biological chemistry Medium 12426321
2018 TIAR accumulates in nuclear foci (G2/M transition granules, GMGs) during late G2/prophase under replication stress; GMGs contain CDK1, and TIAR retains CDK1 in these granules to attenuate its activity; depletion of TIAR accelerates mitotic entry and causes chromosomal instability that is rescued by co-depletion of Cdc25B or CDK1 inhibition. Immunofluorescence time-course, TIAR siRNA, genetic epistasis with Cdc25B/CDK1, CDK1 activity assays EMBO reports High 30538118
2014 In BCR-ABL1-positive CML cells, ER stress promotes cytosolic localization of TIAR, its binding to BRCA1 mRNA 3'-UTR, and formation of a TIAR-HuR complex; TIAR negatively regulates BRCA1 mRNA translation (demonstrated by polysome profiling and luciferase-BRCA1 3'-UTR reporter), and TIAR silencing strongly elevates BRCA1 protein levels. Polysome profiling, luciferase-3'UTR reporter, RNA immunoprecipitation, TIAR siRNA knockdown, subcellular fractionation Cell cycle (Georgetown, Tex.) High 25483082
2010 Under acute/severe hypoxia, TIAR and TIA-1 co-aggregate into stress granules (co-staining with eIF3η); HIF-1α expression is blocked in cells displaying TIAR/TIA-1 granules; TIAR/TIA-1 silencing upregulates HIF-1α; ARE in HIF-1α 3'-UTR drives TIAR-dependent translational suppression in reporter assays. Immunofluorescence, siRNA knockdown, HIF-1α reporter with 3'-UTR ARE, western blot Journal of molecular cell biology Medium 20980400
2016 LncRNA MT1JP interacts with TIAR (RNA-binding protein) to enhance translation of p53 mRNA; MT1JP down-regulation reduces p53 protein without affecting mRNA, and this effect is mediated through TIAR. RNA pull-down, RIP, polysome analysis, siRNA knockdown, luciferase reporter Oncotarget Medium 26909858
2023 In vivo PAR-CLIP (viP-CLIP) in mouse liver identified Insig2 and ApoB mRNAs as prominent TIAL1 targets; TIAL1 influences their translation in hepatocytes; Tial1 mutant mice exhibit altered cholesterol synthesis, APOB secretion, and plasma cholesterol levels, placing TIAL1 in negative feedback regulation of cholesterol biosynthesis. In vivo PAR-CLIP in liver tissue, translation assays in hepatocytes, Tial1 mutant mice with cholesterol phenotyping Nature communications High 37296170
2023 TIAR binds the 5' stem-loop (ε) of HBV pregenomic RNA (pgRNA) and differentially regulates translation: TIAR increases Pol translation while decreasing Cp translation from the same pgRNA; HBV replication or Cp expression induces TIAR nuclear-to-cytoplasmic redistribution, creating a feedback loop that balances Cp and Pol levels. Ribo-seq, PRM mass spectrometry, RIP, RNA pulldown, Cp/Pol expression measurement, TIAR subcellular redistribution imaging Signal transduction and targeted therapy High 37699883
2022 TIA1 and TIAL1 act as global splicing regulators in pro-B cells, binding 5' splice sites for exon definition to control expression of DNA damage sensors including Chek2 and Rif1; double knockout leads to exacerbated DNA damage, altered p53, and increased cell death. Conditional knockout, RNA-seq, CLIP-seq (binding at 5' splice sites), western blot for DNA damage markers Cell reports High 36543128
2023 TIA1 and TIAL1 are required for germinal center B cell positive selection and differentiation; they control the translational identity of dark- and light-zone GC B cells and enable timely expression of the pro-survival molecule MCL1. Conditional knockout in B cells, germinal center assays, polysome profiling for MCL1, flow cytometry Cellular & molecular immunology High 37474714
2019 C. elegans TIAR-2 undergoes liquid-liquid phase separation via its C-terminal prion-like domain (PrLD) and forms liquid-like granules in vivo that inhibit axon regeneration cell-autonomously; axon injury transiently increases granule number; non-phosphorylatable TIAR-2 variants fail to form granules and cannot inhibit regeneration; tyrosine residues in the PrLD are important for granule formation. In vitro phase separation assay, live imaging of granule dynamics (liquid-like properties), PrLD deletion/tyrosine mutants, phosphorylation mutants, axon regeneration assays in C. elegans Neuron High 31378567
2025 TIAL1 directly interacts with the Hippo pathway component SAV1, disrupting the MST1-SAV1 interaction and thereby suppressing Hippo signaling to activate YAP; this function is independent of TIAL1's RNA-binding activity; extracellular stimuli (energy surplus, EGF) upregulate TIAL1 expression to modulate this pathway. Co-immunoprecipitation, RNA-binding-deficient TIAL1 mutants, MST1-SAV1 interaction assays, YAP activity reporters Oncogene Medium 42032365
2003 DT40 cells require either TIA-1 or TIAR for viability; TIA-1 overexpression in tia-1⁻/⁻tiar⁻/⁺ cells induces efficient splicing of two TIAR alternative exons containing in-frame stop codons, reducing TIAR levels via NMD, revealing a TIA-1-mediated autoregulatory loop that controls TIAR expression at the splicing level. Gene targeting in DT40 cells, RT-PCR, cycloheximide treatment (NMD assay), TIA-1 expression rescue The Journal of biological chemistry Medium 12533540
2025 The first 23 nucleotides of the TIAR 5' UTR are necessary and sufficient to confer resistance to SARS-CoV-2 Nsp1-mediated host translational shutoff; the absence of guanosines within positions 10-18 from the 5' end is the defining sequence feature shared between TIAR 5' UTR and the viral leader that confers Nsp1 resistance. Reporter shutoff assays with TIAR 5' UTR deletion/substitution mutants, sequence comparison with SARS-CoV-2 leader RNA (New York, N.Y.) Medium 41407513
2025 Hypoxia-induced lactylation of HMGB1 at K177 drives its nuclear export in a complex with TIAR, promoting stress granule formation in the cytosol; K177R mutation blocks this HMGB1-TIAR complex export and subsequent SG assembly; other stressors (arsenite, heat shock) trigger TIAR nuclear export and SG assembly independently of HMGB1. Mass spectrometry for lactylation sites, K→R mutagenesis, co-IP of HMGB1-TIAR complex, immunofluorescence of SG formation Advanced science Medium 40788094
2021 PHAROH lncRNA sequesters TIAR via a 71-nt hairpin within PHAROH (identified by RNA-antisense pulldown), preventing TIAR from repressing MYC translation; PHAROH knockout decreases MYC protein without affecting mRNA. RNA-antisense pulldown, MYC protein/mRNA measurement in PHAROH KO cells, rescue by PHAROH re-expression eLife Medium 34002693

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. The Journal of cell biology 1066 10613902
2007 Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly. Proceedings of the National Academy of Sciences of the United States of America 255 17502609
1999 Identification of TIAR as a protein binding to the translational regulatory AU-rich element of tumor necrosis factor alpha mRNA. The Journal of biological chemistry 228 9890998
1996 Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities. The Journal of biological chemistry 196 8576255
2011 Translational coregulation of 5'TOP mRNAs by TIA-1 and TIAR. Genes & development 182 21979918
1998 RNA-binding protein TIAR is essential for primordial germ cell development. Proceedings of the National Academy of Sciences of the United States of America 162 9482885
2002 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. Journal of virology 156 12414941
2007 Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nature structural & molecular biology 155 17486099
2006 Translational repression by RNA-binding protein TIAR. Molecular and cellular biology 130 16537914
2003 The proximal region of the 3'-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U. The Journal of biological chemistry 123 12855701
2001 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. The Journal of biological chemistry 115 11514562
1995 The RNA-binding protein TIAR is translocated from the nucleus to the cytoplasm during Fas-mediated apoptotic cell death. Proceedings of the National Academy of Sciences of the United States of America 114 7533298
2005 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. International journal of cancer 94 15514971
2002 Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis. The EMBO journal 94 12356730
2008 A systematic analysis of intronic sequences downstream of 5' splice sites reveals a widespread role for U-rich motifs and TIA1/TIAL1 proteins in alternative splicing regulation. Genome research 87 18456862
1996 Structure, tissue distribution and genomic organization of the murine RRM-type RNA binding proteins TIA-1 and TIAR. Nucleic acids research 86 8871565
2006 Fas-activated serine/threonine kinase (FAST K) synergizes with TIA-1/TIAR proteins to regulate Fas alternative splicing. The Journal of biological chemistry 72 17135269
2005 Identification of the sequence determinants mediating the nucleo-cytoplasmic shuttling of TIAR and TIA-1 RNA-binding proteins. Journal of cell science 71 16278295
2004 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. Journal of virology 71 15280467
2007 Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Molecular and cellular biology 70 17682065
2003 U1 snRNP-dependent function of TIAR in the regulation of alternative RNA processing of the human calcitonin/CGRP pre-mRNA. Molecular and cellular biology 64 12917321
2016 LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway. Oncotarget 60 26909858
2009 Amyotrophic lateral sclerosis-linked mutant SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR): implications for impaired post-transcriptional regulation of vascular endothelial growth factor. The Journal of biological chemistry 58 19805546
2005 Novel DNA-binding properties of the RNA-binding protein TIAR. Nucleic acids research 58 16091628
2019 Inhibition of Axon Regeneration by Liquid-like TIAR-2 Granules. Neuron 57 31378567
2011 Different modes of interaction by TIAR and HuR with target RNA and DNA. Nucleic acids research 57 21233170
2002 Translational repression of human matrix metalloproteinases-13 by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (TIAR). The Journal of biological chemistry 55 12426321
2014 Downregulation of BRCA1 protein in BCR-ABL1 leukemia cells depends on stress-triggered TIAR-mediated suppression of translation. Cell cycle (Georgetown, Tex.) 50 25483082
2008 Mutation of mapped TIA-1/TIAR binding sites in the 3' terminal stem-loop of West Nile virus minus-strand RNA in an infectious clone negatively affects genomic RNA amplification. Journal of virology 45 18768985
2010 TIAR and TIA-1 mRNA-binding proteins co-aggregate under conditions of rapid oxygen decline and extreme hypoxia and suppress the HIF-1α pathway. Journal of molecular cell biology 40 20980400
2016 The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans. G3 (Bethesda, Md.) 38 26865701
2003 TIA-1 or TIAR is required for DT40 cell viability. The Journal of biological chemistry 31 12533540
2014 HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA. International journal of molecular sciences 30 24566137
2006 Control of the ATP synthase beta subunit expression by RNA-binding proteins TIA-1, TIAR, and HuR. Biochemical and biophysical research communications 27 16890199
2013 Distinct binding properties of TIAR RRMs and linker region. RNA biology 26 23603827
2000 Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury. Journal of neuroscience research 24 10700014
2010 Impaired embryonic development in mice overexpressing the RNA-binding protein TIAR. PloS one 23 20596534
2021 LOXL1-AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR-374b-5p/MMP14 axis. Journal of cellular and molecular medicine 22 34890108
2021 PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR. eLife 18 34002693
2013 The C. elegans TIA-1/TIAR homolog TIAR-1 is required to induce germ cell apoptosis. Genesis (New York, N.Y. : 2000) 17 23913578
2023 The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis. Cellular & molecular immunology 16 37474714
2022 The splicing regulators TIA1 and TIAL1 are required for the expression of the DNA damage repair machinery during B cell lymphopoiesis. Cell reports 16 36543128
2018 TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO reports 16 30538118
2014 The involvement of mRNA processing factors TIA-1, TIAR, and PABP-1 during mammalian hibernation. Cell stress & chaperones 13 24590458
2023 RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation. Signal transduction and targeted therapy 12 37699883
2018 miR‑223‑3p/TIAL1 interaction is involved in the mechanisms associated with the neuroprotective effects of dexmedetomidine on hippocampal neuronal cells in vitro. Molecular medicine reports 12 30569136
2014 Genome-wide profiling reveals a role for T-cell intracellular antigens TIA1 and TIAR in the control of translational specificity in HeLa cells. The Biochemical journal 12 24927121
2005 The RNA binding protein TIAR is involved in the regulation of human iNOS expression. Cellular and molecular biology (Noisy-le-Grand, France) 12 16191398
2016 PTB and TIAR binding to insulin mRNA 3'- and 5'UTRs; implications for insulin biosynthesis and messenger stability. Heliyon 11 27699280
2023 In vivo PAR-CLIP (viP-CLIP) of liver TIAL1 unveils targets regulating cholesterol synthesis and secretion. Nature communications 10 37296170
2015 TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication. Biochemical and biophysical research communications 10 26363455
1998 Increased expression of the TIAR protein in the hippocampus of Alzheimer patients. Neuroreport 9 9631446
2009 Splicing of the large intron present in the nonstructural gene of minute virus of mice is governed by TIA-1/TIAR binding downstream of the nonconsensus donor. Journal of virology 8 19339348
2016 Genome-wide analysis of TIAR RNA ligands in mouse macrophages before and after LPS stimulation. Genomics data 7 26981431
2015 Targeted Knockdown of RNA-Binding Protein TIAR for Promoting Self-Renewal and Attenuating Differentiation of Mouse Embryonic Stem Cells. Stem cells international 7 25918534
2010 Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid tissues from adolescents with immune and non-immune thyroid diseases. Folia histochemica et cytobiologica 7 20675271
2023 TIAR and FMRP shape pro-survival nascent proteome of leukemia cells in the bone marrow microenvironment. iScience 6 37123244
2022 The TIAR-mediated Nrf2 response to oxidative stress is mediated through the Nrf2 noncoding 3'untranslated region in Spodoptera litura. Free radical biology & medicine 6 35367339
2023 The stress granule component TIAR during the non-embryonic development of the colonial ascidian Botryllusschlosseri. Fish & shellfish immunology 5 37604264
2021 MBNL1 Suppressed Cancer Metastatic of Skin Squamous Cell Carcinoma Via by TIAL1/MYOD1/Caspase-9/3 Signaling Pathways. Technology in cancer research & treatment 5 33896245
2025 Lactylation of HMGB1 at K177 Drives Nuclear Export of TIAR to Promote Hypoxia-Induced Stress Granule Formation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40788094
2023 Depletion of TIAR impairs embryogenesis via inhibiting zygote genome transcribe. Reproduction in domestic animals = Zuchthygiene 3 37667420
2023 Two predicted α-helices within the prion-like domain of TIAR-1 play a crucial role in its association with stress granules in Caenorhabditis elegans. Frontiers in cell and developmental biology 3 38161334
2026 Escape from SARS-CoV-2 Nsp1-mediated host shutoff by TIAR transcript reveals general features of Nsp1 resistance. RNA (New York, N.Y.) 0 41407513
2026 TIAL1 regulates the Hippo pathway through an RNA-binding-independent mechanism. Oncogene 0 42032365