Affinage

BUD13

BUD13 homolog · UniProt Q9BRD0

Length
619 aa
Mass
70.5 kDa
Annotated
2026-06-09
22 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BUD13 is an RNA-binding component of the retention and splicing (RES) complex that promotes productive pre-mRNA splicing by antagonizing intron retention at a defined subset of introns, most clearly demonstrated at Irf7, where its loss reduces mature transcript and protein output and dampens the type I interferon response, impairing macrophage antiviral resistance (PMID:30639243, PMID:35670808). Consistent with this role, human BUD13 loss-of-function elevates global intron retention, reduces spliceosomal protein levels, and produces nuclear morphology defects that are rescued by re-expression of BUD13 (PMID:35670808). Beyond splicing, BUD13 acts as an endogenous inhibitor of the Fbw7–Cul1 ubiquitin ligase by stabilizing Fbw7 oncogenic substrates and interfering with Fbw7–Cul1 complex formation, a function regulated by RSK3-mediated phosphorylation; cancer-associated mutations (R156C, R230Q) evade this phosphorylation and confer gain-of-oncogenic function in colon cancer (PMID:37382881). BUD13 is itself subject to m6A regulation by METTL3 and is recruited by various non-coding RNAs to stabilize target mRNAs in tumor contexts (PMID:36463205). Loss-of-function BUD13 variants co-segregate with specific language impairment in humans, with a corresponding neural phenotype in an animal model (PMID:35053791).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2019 High

    Established that BUD13 is a sequence-context-selective RNA-binding factor that resolves intron retention, linking its splicing activity to a concrete physiological output (innate antiviral immunity).

    Evidence BUD13 CLIP plus knockdown with global intron-retention RNA-seq, transcript/protein quantification, and VSV infection assay in macrophages

    PMID:30639243

    Open questions at the time
    • Does not define the full set of BUD13-dependent introns or the sequence determinant of selectivity
    • RES-complex partner requirements for intron resolution not dissected
  2. 2021 Medium

    Connected BUD13 to the RES complex and to a human neurodevelopmental phenotype, extending its relevance from cell biology to organism-level function.

    Evidence Whole-exome sequencing with co-segregation analysis in families and an animal loss-of-function model

    PMID:35053791

    Open questions at the time
    • Mechanistic link between splicing defects and the neural phenotype not established
    • Abstract-level mechanistic detail
  3. 2022 High

    Showed that human BUD13 loss-of-function causes global splicing failure, spliceosomal protein depletion, and nuclear structural defects, confirming its RES-complex role in patient cells.

    Evidence Patient exome sequencing, RNA-seq, proteomics, electron microscopy, and overexpression rescue in dermal fibroblasts

    PMID:35670808

    Open questions at the time
    • Causal chain from splicing loss to nuclear invaginations not resolved
    • Single-lab patient cohort
  4. 2022 Medium

    Identified a regulatory and effector axis in which BUD13 is stabilized by METTL3 m6A methylation and in turn stabilizes downstream mRNA targets, implicating BUD13 in mRNA stability control beyond splicing.

    Evidence m6A and mRNA stability assays with knockdown/overexpression and xenograft model in glioblastoma

    PMID:36463205

    Open questions at the time
    • Direct biochemical reconstitution of BUD13-mediated mRNA stabilization lacking
    • Whether stabilization requires the RES complex unknown
  5. 2023 Medium

    Revealed a non-splicing role for BUD13 as an endogenous inhibitor of the Fbw7–Cul1 ligase, and showed how cancer-associated mutations convert it into an oncogenic driver by evading RSK3 phosphorylation.

    Evidence Somatic mutation analysis, RSK3 kinase assays, Fbw7–Cul1 co-immunoprecipitation, and oncogenicity assays in colon cancer models

    PMID:37382881

    Open questions at the time
    • Co-IP for complex disruption without reciprocal/structural validation
    • How phosphorylation status controls Fbw7 binding not mechanistically defined
  6. 2023 Low

    Extended the mRNA-stabilization model to additional non-coding-RNA-recruited contexts, framing BUD13 as a recruitable mRNA-stabilizing factor in cancer.

    Evidence ChIP, RIP, RNA pulldown, FISH, and mRNA stability assays in colorectal cancer cells

    PMID:38053379

    Open questions at the time
    • RIP/pulldown without independent replication
    • Direct binding of BUD13 to target mRNA versus indirect recruitment unresolved
  7. 2024 Low

    Reported circRNA-mediated recruitment of BUD13 to the KEAP1/NRF2/HO-1 pathway in kidney injury, suggesting context-dependent roles in oxidative-stress signaling.

    Evidence RIP, gain/loss-of-function assays, FISH, in LPS-stimulated HK-2 cells and CLP rat models

    PMID:39289683

    Open questions at the time
    • BUD13's direct biochemical role in the pathway not characterized
    • Single lab, mechanism inferred from recruitment

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BUD13's splicing/RES-complex activity mechanistically relates to its reported mRNA-stabilization and Fbw7-inhibitory functions remains unresolved.
  • No unified model linking nuclear splicing role to cytoplasmic/non-coding-RNA-recruited stabilization
  • Structural basis of RES-complex incorporation and Fbw7 binding undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
CUL1FBXW7RSK3
Complex memberships
RES complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 BUD13 acts as an RNA-binding protein that binds to a specific retained intron in Irf7 pre-mRNA and promotes successful splicing, thereby antagonizing intron retention; BUD13 deficiency increases intron retention at a subset of introns sharing characteristics with the Irf7 intron, reduces mature Irf7 transcript and protein levels, and consequently dampens the type I interferon response, impairing macrophage resistance to VSV infection. BUD13 knockdown with RNA-seq (global intron retention analysis), BUD13 RNA cross-linking (CLIP), mature transcript/protein quantification, viral infection assay Molecular cell High 30639243
2022 BUD13 loss-of-function (via a homozygous nonsense variant causing alternative splicing to a truncated isoform) in human patients leads to elevated global intron retention, a global reduction of spliceosomal proteins, and nuclear morphology defects (multiple nuclear invaginations) in dermal fibroblasts; overexpression of either BUD13 isoform normalized nuclear morphology, placing BUD13 in the retention and splicing (RES) complex. Exome sequencing of patients, RNA sequencing, proteomics, immunoblotting, immunostaining, electron microscopy, overexpression rescue assay Genetics in medicine High 35670808
2023 BUD13 functions as an endogenous inhibitor of the E3 ubiquitin ligase Fbw7 by stabilizing Fbw7's oncogenic substrates; cancer-associated BUD13 mutations R156C and R230Q evade RSK3-mediated phosphorylation, enhance oncogenicity, and interfere with Fbw7–Cul1 complex formation, thereby promoting colon cancer growth. BUD13 regulation is also critical in the mTOR inhibition response. Algorithm-based somatic mutation analysis, validation of phosphorylation evasion (RSK3 kinase assays), Fbw7–Cul1 co-immunoprecipitation, oncogenicity assays in colon cancer models The Journal of experimental medicine Medium 37382881
2022 In glioblastoma cells, METTL3-mediated m6A methylation stabilizes BUD13 mRNA and upregulates BUD13 expression; BUD13 in turn stabilizes CDK12 mRNA, leading to CDK12-mediated phosphorylation of MBNL1, which promotes vasculogenic mimicry formation. m6A methylation assay, mRNA stability assay, knockdown/overexpression functional studies, subcutaneous tumor xenograft model Cell death & disease Medium 36463205
2020 BUD13 binds to the lncRNA DBH-AS1 and stabilizes FN1 mRNA; DBH-AS1 recruits BUD13 to mediate FN1 expression, forming a DBH-AS1/BUD13/FN1 regulatory axis that promotes proliferation, migration, and invasion of DLBCL cells. RNA immunoprecipitation (RIP), RNA pulldown, mRNA stability assay, rescue/loss-of-function experiments Cell biology international Low 32091157
2021 BUD13 is identified as a component of the retention and splicing (RES) complex, and rare loss-of-function variants in BUD13 co-segregate with specific language impairment (SLI) in humans; loss-of-function mutations in BUD13 in an animal model caused a profound neural phenotype. Whole-exome sequencing, Sanger sequencing validation, co-segregation analysis, animal model loss-of-function Brain sciences Medium 35053791
2024 In sepsis-associated acute kidney injury models, circ_001653 recruits BUD13 to activate the KEAP1/NRF2/HO-1 signaling pathway, thereby modulating apoptosis, inflammation, and oxidative stress in renal tubular epithelial cells. RIP, gain/loss-of-function assays, in vitro (LPS-stimulated HK-2 cells) and in vivo (CLP rat) models, subcellular fractionation/FISH for localization Journal of inflammation Low 39289683
2023 BUD13 is recruited by lncRNA RNASEH1-AS1 to stabilize ANXA2 mRNA, activating the Wnt/β-catenin pathway and promoting colorectal cancer progression; CBP-mediated H3K27ac drives RNASEH1-AS1 expression upstream of this axis. ChIP, RIP, RNA pulldown, nucleoplasmic separation/FISH, mRNA stability assay, functional cancer cell assays Neoplasma Low 38053379

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Association and interaction of APOA5, BUD13, CETP, LIPA and health-related behavior with metabolic syndrome in a Taiwanese population. Scientific reports 49 27827461
2019 BUD13 Promotes a Type I Interferon Response by Countering Intron Retention in Irf7. Molecular cell 40 30639243
2014 Association of the variants in the BUD13-ZNF259 genes and the risk of hyperlipidaemia. Journal of cellular and molecular medicine 38 24780069
2020 Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13. Cell biology international 25 32091157
2014 Association between the MLX interacting protein-like, BUD13 homolog and zinc finger protein 259 gene polymorphisms and serum lipid levels. Scientific reports 25 24989072
2021 CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13. Journal of translational medicine 22 34861864
2015 Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population. PloS one 20 26397108
2022 The mechanism of BUD13 m6A methylation mediated MBNL1-phosphorylation by CDK12 regulating the vasculogenic mimicry in glioblastoma cells. Cell death & disease 19 36463205
2017 Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal. PloS one 18 28245265
2021 Family-Based Whole-Exome Analysis of Specific Language Impairment (SLI) Identifies Rare Variants in BUD13, a Component of the Retention and Splicing (RES) Complex. Brain sciences 16 35053791
2019 Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and structure of APOA5 with increased plasma triglyceride levels in a Korean population. Scientific reports 15 31165758
2021 Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study. Scientific reports 13 33986338
2019 Functional polymorphisms of the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster are associated with dyslipidemia in a sex-specific pattern. PeerJ 12 30631647
2024 Circ_001653 alleviates sepsis associated-acute kidney injury by recruiting BUD13 to regulate KEAP1/NRF2/HO-1 signaling pathway. Journal of inflammation (London, England) 10 39289683
2019 Interaction of polymorphisms in APOA4-APOA5-ZPR1-BUD13 gene cluster and sleep duration on 5-year lipid changes in middle aged and older Chinese. Sleep 8 31181149
2015 Association study of BUD13-ZNF259 gene rs964184 polymorphism and hemorrhagic stroke risk. International journal of clinical and experimental medicine 8 26885234
2022 Alternative splicing of BUD13 determines the severity of a developmental disorder with lipodystrophy and progeroid features. Genetics in medicine : official journal of the American College of Medical Genetics 5 35670808
2015 Differential Lipid Response to Statins Is Associated With Variants in the BUD13-APOA5 Gene Region. Journal of cardiovascular pharmacology 5 25900265
2023 Somatic gain-of-function mutations in BUD13 promote oncogenesis by disrupting Fbw7 function. The Journal of experimental medicine 3 37382881
2023 Regularized Machine Learning Models for Prediction of Metabolic Syndrome Using GCKR, APOA5, and BUD13 Gene Variants: Tehran Cardiometabolic Genetic Study. Cell journal 2 37641415
2025 Genome-wide study links cardiometabolic factors to cognition via APOA4-APOA5-ZPR1-BUD13 and other loci in rural Indians. Alzheimer's & dementia : the journal of the Alzheimer's Association 1 40665476
2023 RNASEH1-AS1 induced by H3K27ac stabilizes ANXA2 mRNA to promote the progression of colorectal cancer through recruiting BUD13. Neoplasma 0 38053379

Missed literature

Know a paper Affinage missed for BUD13? Flag it for the maintainers and the community.

No submissions yet.