| 2013 |
Arid5a is an RNA-binding protein that stabilizes IL-6 mRNA by binding to its 3' untranslated region, counteracting the destabilizing effect of the ribonuclease Regnase-1, thereby promoting elevation of IL-6 serum levels in vivo. |
RNA binding assays, Arid5a-deficient mice, LPS challenge model, mRNA stability assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23676272
|
| 2011 |
Arid5a physically interacts with Sox9 in the nucleus, binds directly to the Col2a1 gene promoter, stimulates histone H3 acetylation at that region, and cooperatively enhances chondrocyte-specific transcription and differentiation. |
Co-immunoprecipitation, ChIP, overexpression and knockdown in ATDC5 cells, organ culture |
Molecular biology of the cell |
High |
21346191
|
| 2016 |
Arid5a selectively stabilizes Stat3 mRNA (but not Stat1 or Stat5 mRNA) in CD4+ T cells in an IL-6-dependent manner, directing naive CD4+ T cells toward Th17 differentiation; loss of Arid5a reduces STAT3 levels and shifts cells toward IL-10-expressing anti-inflammatory fate. |
Arid5a-deficient mice, mRNA stability assays, Th17 polarization assays, flow cytometry |
The Journal of experimental medicine |
High |
27022145
|
| 2016 |
Arid5a binds to a conserved stem-loop structure in the 3'UTR of T-bet mRNA and stabilizes it in Th1 cells, thereby promoting IFN-γ production and contributing to septic shock; Arid5a-deficient mice are resistant to LPS-induced endotoxic shock with reduced IFN-γ and IL-6. |
RNA binding assays (stem-loop structure), Arid5a KO mice, LPS/P. acnes endotoxic shock models, cytokine measurement |
Proceedings of the National Academy of Sciences of the United States of America |
High |
27671645
|
| 2017 |
During LPS stimulation, NF-κB activates Arid5a gene expression (promoting IL-6 mRNA stabilization), while in the late phase p38 MAPK phosphorylates Arid5a and recruits the E3 ubiquitin ligase WWP1, which ubiquitinates Arid5a via K48-linked chains leading to its proteasomal degradation; additionally, AUF-1 destabilizes Arid5a mRNA via AU-rich elements in its 3'UTR. |
Phosphorylation assays, ubiquitination assays, NF-κB/MAPK pathway inhibitors, mutagenesis blocking phosphorylation, mRNA stability assays |
Nucleic acids research |
High |
28168301
|
| 2018 |
IL-17 signaling induces Arid5a expression; Arid5a is recruited to the adaptor TRAF2, stabilizes IL-17-induced cytokine transcripts by binding their 3'UTRs, counteracts MCPIP1 (Regnase-1)-mediated mRNA degradation, and associates with the eukaryotic translation initiation complex to facilitate translation of the transcription factors IκBζ and C/EBPβ, creating a feed-forward amplification loop. |
Co-immunoprecipitation (TRAF2, eIF complex), mRNA stability assays, translation assays, Arid5a KO cells |
Science signaling |
High |
30301788
|
| 2018 |
Arid5a stabilizes OX40 mRNA in CD4+ T cells by recognizing an alternative decay element (ADE)-like stem-loop structure in the OX40 3'UTR, and impairs the RNA-destabilizing functions of both Regnase-1 and Roquin-1 on this target. |
RNA binding assays, stem-loop mutagenesis, Arid5a KO mice, EAE model, adoptive transfer |
European journal of immunology |
High |
29244194
|
| 2018 |
Arid5a is present in both cytoplasm and nucleus of resting cells; upon inflammatory stimulation it is imported into the nucleus via the classical importin-α/β1 pathway, and subsequently exported to the cytoplasm via CRM1-dependent nuclear export; cytoplasmic Arid5a is associated with UPF1 (up-frameshift protein 1). This stimulus-dependent nuclear-cytoplasmic shuttling is required for its dual function in mRNA stabilization and transcriptional regulation. |
Transgenic mice, nuclear fractionation, importin pathway inhibitors (importazole), CRM1 inhibitor (leptomycin B), co-immunoprecipitation with UPF1 |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29358370
|
| 2019 |
Arid5a represses transcription of Ppar-γ2, acting as a negative regulator of adipogenesis; in the absence of Arid5a, persistent Ppar-γ2 expression drives adipocyte differentiation and enhanced fatty acid uptake. Arid5a and Ppar-γ2 are dynamically counter-regulated by each other to maintain adipose tissue homeostasis. |
Arid5a KO mice (adult-onset obesity), Arid5a transgenic mice (diet-induced obesity resistance), 3T3-L1 differentiation assays, gene expression analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
31289228
|
| 2021 |
Arid5a stabilizes Ido1 (indoleamine 2,3-dioxygenase 1) and Ccl2 mRNAs in tumor cells, augmenting tryptophan catabolism and creating an immunosuppressive tumor microenvironment that promotes immune evasion; deletion of Arid5a in tumor cells enhances antitumor immunity in immunocompetent but not immunodeficient mice. |
Arid5a KO tumor cell lines, mRNA stability assays, syngeneic mouse tumor models, immune cell profiling |
Cancer immunology research |
High |
34006522
|
| 2021 |
IL-6-induced Arid5a promotes transcription of the lncRNA AU021063, which in turn stabilizes Trib3 and activates Mek/Erk signaling to drive breast cancer metastasis; genetic ablation of Arid5a abolishes this cascade. |
Arid5a KO, RNA stability assays, in vitro invasion assays, mouse metastasis models |
Cancer letters |
Medium |
34389433
|
| 2005 |
MRF1 (ARID5A) binds to both the N-terminal and C-terminal regions of ERα in an estradiol-independent manner (also interacts with thyroid receptor α, RXRα, and androgen receptor in ligand-dependent manner), has intrinsic repressor activity, and represses ERα-mediated transcriptional activation in a dose-dependent manner without requiring histone deacetylase activity. |
Yeast two-hybrid screen, co-immunoprecipitation, recombinant protein binding assays, transient transfection reporter assays, GAL4 reporter assay |
Molecular endocrinology |
High |
15941852
|
| 2014 |
ARID5A is induced by IL-6 in CD4+ T cells via a STAT3-dependent mechanism; ARID5A physically associates with RORγt through its N-terminal region and acts as a negative regulator of RORγt-induced Th17 cell differentiation and IL-17A promoter activation. |
Co-immunoprecipitation, overexpression in murine CD4+ T cells, IL-17A promoter reporter assay, flow cytometry |
Arthritis & rheumatology |
Medium |
24782182
|
| 2020 |
Noncanonical phosphorylation of STAT1 at Thr749 (mediated by a TBK1-IKKβ complex downstream of TLR4 endocytosis) drives STAT1 binding to a noncanonical DNA motif (5'-TTTGANNC-3') in the ARID5A promoter, thereby activating ARID5A expression and downstream IL-6 mRNA stabilization. |
Site-specific mutagenesis, ChIP, kinase inhibitors, TLR4 endocytosis manipulation, ARID5A promoter reporter assays |
Science signaling |
High |
32209697
|
| 2020 |
β-catenin-mediated transcriptional activation of FOSL2 and repression of ARID5A together drive M1-to-M2 TAM polarization in lung cancer; pharmacological or genetic ablation of β-catenin reprograms M2-like TAMs to M1-like TAMs and suppresses tumor growth. |
Pharmacological β-catenin inhibition, macrophage-specific genetic ablation, transcriptome analysis, in vitro TAM model, in vivo lung tumor models |
Science advances |
Medium |
32548260
|
| 2024 |
Using NMR-centered biochemistry, the Arid5a ARID domain was found to bind DNA with a defined preference; high-throughput in vitro binding defined a consensus RNA-binding motif engaged by the core ARID domain; iCLIP2 revealed transcriptome-wide binding preference for (A)U-rich regions in pre-mRNA transcripts; intrinsically disordered regions (IDRs) flanking the ARID domain modulate DNA-binding specificity and affinity, and are crucial for RNA interactions. |
NMR spectroscopy, high-throughput in vitro binding (RBNS), iCLIP2, mutagenesis of IDR extensions |
The Journal of biological chemistry |
High |
38866324
|
| 2024 |
ARID5A stabilizes IDO1 mRNA in colorectal cancer cells, leading to upregulation of IDO1 expression, tryptophan-to-kynurenine conversion, kynurenine-mediated AhR activation in CAR-T cells, and consequent CAR-T cell exhaustion; targeting the ARID5A-IDO1-AhR axis with AhR or IDO1 inhibitors alleviates T cell exhaustion. |
ARID5A overexpression, mRNA stability assays, CAR-T co-culture assays, AhR/IDO1 inhibitor treatment |
Translational oncology |
Medium |
38316094
|
| 2024 |
Transcriptome-wide RIP-Seq revealed that Arid5a inducibly interacts with IL-17 target mRNAs including CEBPB and CEBPD, as well as rRNAs including 18S rRNA (a 40S ribosome constituent); IL-17 promotes Arid5a nuclear export and association with 18S rRNA; Arid5a-deficient cells show repressed global protein synthesis, with C/EBPs controlled at the translational rather than mRNA level, establishing Arid5a as a ribosome-associated translational regulator. |
RIP-Seq, Arid5a KO mice, AGN mouse model, fractionation, polysome profiling, CRISPR-Cas9 KO |
The Journal of experimental medicine |
High |
39058386
|
| 2025 |
ARID5A epi-transcriptionally stabilizes MAVS (Mitochondrial Antiviral Signaling Protein) mRNA in cardiomyocytes of aged hearts, leading to NF-κB and TBK1 activation and amplifying cardiac aging and inflammation; lentiviral shRNA targeting ARID5A in aged mouse myocardium mitigated inflammatory and aging phenotypes and improved cardiac function. |
Single-cell RNA-seq of human heart tissues, ARID5A-MAVS RNA binding/stability assays, lentiviral shRNA gene therapy in aged mice, NF-κB/TBK1 pathway analysis |
Nature cardiovascular research |
High |
40301689
|
| 2025 |
In skeletal muscle, Arid5a functions as a transcriptional repressor of the lipid uptake genes Cd36 and Fabp4, downstream of glucocorticoid receptor (GR) transactivation; Arid5a is required and sufficient to reduce muscle triacylglycerol accumulation, acting as a pro-metabolic effector. |
GR knock-in mice (rs6190), myotropic AAV overexpression/knockdown in muscle, RNA-seq and ChIP-seq, metabolic phenotyping |
Science advances |
Medium |
40632872
|
| 2026 |
TNF upregulates Arid5a expression through the NF-κB1/TRAF2 pathway, causing cytoplasmic relocalization of Arid5a; Arid5a then stabilizes proinflammatory transcripts and enhances expression of chemokines driving rheumatoid arthritis; Arid5a-deficient mice are resistant to collagen-induced arthritis with reduced Th17 cells in synovial tissue. |
TRAF2 KO cells, NF-κB/IKK inhibitors, NIK inhibitors, Arid5a KO mice, collagen-induced arthritis model, mRNA stability assays |
JCI insight |
High |
41574607
|
| 2022 |
Rbpjl binds to the promoter region of Arid5a and transcriptionally represses its expression, thereby suppressing the Arid5a/IL-6/STAT3 signaling axis and alleviating pancreatic acinar cell inflammation in acute pancreatitis. |
ChIP, EMSA, dual-luciferase reporter assays, Rbpjl overexpression/knockdown, LPS-induced cell model, cerulein-induced AP mouse model |
Cell & bioscience |
Medium |
35725649
|
| 2020 |
β2-adrenergic receptor stimulation activates the cAMP/PKA/CREB pathway in cardiac fibroblasts, phosphorylating CREB and inducing Arid5a expression; Arid5a in turn stabilizes IL-6 mRNA, and this pathway is required for β2AR-mediated IL-6 production (abolished in Arid5a KO cardiac fibroblasts). |
Arid5a KO cardiac fibroblasts, β2AR agonists, adenylate cyclase activators, PKA inhibitors, CREB activity assays, ELISA |
Pharmacology research & perspectives |
Medium |
32302067
|