Affinage

YAE1

Protein YAE1 homolog · UniProt Q9NRH1

Length
226 aa
Mass
25.3 kDa
Annotated
2026-06-11
11 papers in source corpus 5 papers cited in narrative 5 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

YAE1 (human YAE1D1) is a target-specific adaptor that delivers apo-ABCE1/Rli1 to the cytosolic iron-sulfur protein assembly (CIA) machinery for [4Fe-4S] cluster insertion (PMID:26182403). It functions in a heterodimer with LTO1/ORAOV1, with deca-GX3 motifs in both proteins mediating their association and the LTO1 C-terminal tryptophan contacting the CIA targeting complex, while YAE1 itself directly recruits the ABCE1 client to form a trimeric LTO1–YAE1–ABCE1 complex (PMID:26182403, PMID:23318452). By maintaining ABCE1 cluster integrity under aerobic conditions, this complex is required for 60S ribosomal subunit maturation and translation initiation (PMID:23318452). The adaptor module is functionally conserved: human YAE1D1 and ORAOV1 complement loss of the yeast factors (PMID:26182403, PMID:23318452). Through its control of ABCE1, the LTO1/YAE1 complex acts upstream in the nonsense-mediated mRNA decay (NMD) pathway, and its loss impairs NMD, derepressing the MHC-I regulators NLRC5, IRF1, and NF-κB and thereby enhancing antigen presentation and T cell-mediated killing of tumor cells (PMID:40987494).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2013 High

    Established that Yae1 physically bridges Lto1 and Rli1/ABCE1 into a trimeric complex whose loss disrupts ribosome biogenesis, linking the factor to translation rather than a vague cellular role.

    Evidence Yeast conditional mutants with sucrose-gradient ribosome maturation assays, in vivo/in vitro interaction assays, and human ORAOV1 complementation

    PMID:23318452

    Open questions at the time
    • Did not resolve the molecular basis of how each interaction is configured
    • Mechanism by which the complex preserves the [4Fe-4S] cluster under aerobic stress not defined at atomic level
  2. 2015 High

    Defined the molecular logic of the adaptor: it answered how a generic CIA machinery achieves client specificity, showing Yae1-Lto1 act as a dedicated targeting module for apo-Rli1.

    Evidence Protein interaction screens, domain mutagenesis of the Lto1 C-terminal tryptophan and deca-GX3 motifs, Fe-S maturation assays, and cross-species complementation with human YAE1D1

    PMID:26182403

    Open questions at the time
    • No structural model of the assembled complex
    • Whether other CIA clients use analogous dedicated adaptors not addressed
  3. 2025 High

    Placed the LTO1/YAE1 complex in a disease-relevant pathway, showing that via ABCE1 it sustains NMD and thereby restrains MHC-I antigen presentation in tumor cells.

    Evidence CRISPR knockouts, fluorescent NMD reporters, polysome profiling, mRNA decay assays, TCR-T/tumor coculture killing, and a mouse tumor model

    PMID:40987494

    Open questions at the time
    • Whether the NMD effect is solely via ABCE1 cluster maturation or involves additional clients
    • Direct biochemical demonstration that YAE1 loss reduces ABCE1 cluster occupancy in this context not shown
  4. 2026 Medium

    Showed the Yae1 domain is a separable, essential functional module by identifying it as a C-terminal domain of S. pombe Tpt1 that can be supplied in trans.

    Evidence Domain deletion/mutagenesis and split-domain genetic complementation in S. pombe growth assays

    PMID:41339091

    Open questions at the time
    • Limited to fission yeast; relevance of the Tpt1 fusion arrangement to other organisms unclear
    • Does not establish whether the fused arrangement confers any functional coupling to RNA 2'-phosphotransferase activity
  5. 2016 Low

    Identified YAE1 as genetically required for tolerance to the antifungal vulpinic acid, but without resolving a direct mechanistic link.

    Evidence Chemical-genetic haploinsufficiency/homozygous profiling, flow cytometry cell cycle analysis, and gene expression measurement in yeast

    PMID:27660105

    Open questions at the time
    • Single-method chemogenomic screen with no mechanistic connection between YAE1 function and vulpinic acid
    • Cause of S and G2/M arrest not linked to a defined YAE1 activity

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of the assembled LTO1–YAE1–ABCE1/CIA complex and the precise step at which YAE1 hands apo-ABCE1 to the CIA targeting machinery remain undefined.
  • No experimental structure of the trimeric adaptor complex
  • Whether YAE1 has clients beyond ABCE1 is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 1
Pathway
GO:0140098 catalytic activity, acting on RNA 1
Partners
ABCE1LTO1ORAOV1RLI1
Complex memberships
LTO1-YAE1-ABCE1 adaptor complex

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Yae1 and Lto1 form a complex that functions as a target-specific adaptor recruiting apo-Rli1 to the generic CIA (cytosolic Fe-S protein assembly) machinery for iron-sulfur cluster insertion. Lto1 uses its conserved C-terminal tryptophan to bind the CIA targeting complex, deca-GX3 motifs in both Yae1 and Lto1 mediate their complex formation, and Yae1 directly recruits Rli1. Human YAE1D1 can replace yeast Yae1, demonstrating evolutionary conservation. Systematic protein interaction approaches (Co-IP/pulldown), yeast depletion/complementation experiments, domain mutagenesis (C-terminal tryptophan, deca-GX3 motifs), Fe-S cluster maturation assays eLife High 26182403
2013 Yae1 bridges the interaction between Lto1 (YNL260c/ORAOV1) and Rli1/ABCE1, forming a trimeric complex. Loss of Lto1 (and by extension this complex) leads to defective 60S ribosomal subunit maturation and abrogated translation initiation. The complex is required for maintaining Rli1/ABCE1 [4Fe-4S] cluster integrity under aerobic conditions. Interactions were demonstrated both in vivo and in vitro. Yeast conditional mutants, ribosome maturation assays (sucrose gradient fractionation), in vivo and in vitro protein interaction assays (Co-IP, pulldown), genetic complementation with human ORAOV1 Oncogene High 23318452
2025 The LTO1/YAE1 complex regulates nonsense-mediated RNA decay (NMD) and MHC-I antigen presentation in tumor cells. Deficiency of LTO1, YAE1, or their downstream target ABCE1 impairs NMD, causing overexpression of MHC-I regulators NLRC5, IRF1, and NF-κB, resulting in enhanced T cell activation and tumor cell killing. The complex acts upstream of ABCE1 in the NMD pathway. CRISPR/Cas9 knockouts, overexpression, mutational analysis, fluorescent NMD reporter assays, FACS, RT-qPCR, mRNA decay assays, polysome profiling, TCR-T cell/tumor coculture killing assays, mouse tumor model Journal for immunotherapy of cancer High 40987494
2026 In fission yeast Schizosaccharomyces pombe, Tpt1 contains a C-terminal domain (aa 238-365) homologous to budding yeast iron-sulfur cluster assembly factor Yae1. Both the RNA 2'-phosphotransferase catalytic domain and the C-terminal Yae1 domain of SpTpt1 are essential for S. pombe growth, though they need not be covalently linked within the same polypeptide. This identifies the Yae1 domain as a functionally essential, separable module. Domain deletion/mutational analysis, genetic complementation (split-domain rescue), S. pombe growth assays, sequence homology analysis RNA (New York, N.Y.) Medium 41339091
2016 Yeast strains lacking YAE1 are hypersensitive to the antifungal compound vulpinic acid, and vulpinic acid treatment significantly lowers YAE1 expression; cell cycle arrest in S and G2/M phases is observed under these conditions. Haploinsufficiency and homozygous-profiling chemical-genetic assays, flow cytometry cell cycle analysis, relative gene expression measurement Journal of applied microbiology Low 27660105

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion. eLife 53 26182403
2013 The function of ORAOV1/LTO1, a gene that is overexpressed frequently in cancer: essential roles in the function and biogenesis of the ribosome. Oncogene 34 23318452
2016 Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and Induces Apoptosis in Human Oligodendroglia Cells. International journal of molecular sciences 23 27023521
2005 Identification of mouse blastocyst genes that are downregulated by double-stranded RNA-mediated knockdown of Oct-4 expression. Molecular reproduction and development 16 15685634
2019 Can social support during pregnancy affect maternal DNA methylation? Findings from a cohort of African-Americans. Pediatric research 11 31349361
2016 A chemogenomic approach to understand the antifungal action of Lichen-derived vulpinic acid. Journal of applied microbiology 7 27660105
2022 In silico analysis of genomic landscape of SARS-CoV-2 and its variant of concerns (Delta and Omicron) reveals changes in the coding potential of miRNAs and their target genes. Gene 6 36470485
2018 A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE). American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 4 30556296
2025 CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma. Oncology research 1 41502527
2026 Fission yeast Tpt1 is composed of tandem RNA 2'-phosphotransferase and Yae1 domains, both of which are essential for viability. RNA (New York, N.Y.) 0 41339091
2025 LTO1 and YAE1 regulate MHC-I expression via nonsense-mediated RNA decay in tumor cells. Journal for immunotherapy of cancer 0 40987494

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