Affinage

LIAT1

Protein LIAT1 · UniProt Q6ZQX7

Length
453 aa
Mass
49.7 kDa
Annotated
2026-04-28
5 papers in source corpus 3 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIAT1 is an intrinsically disordered protein that functions as a positive regulator of the arginyltransferase Ate1, binding Ate1 through a conserved ~30-residue region with isoform-selective affinity and stimulating N-terminal arginylation of substrates in vitro (PMID:25369936). Its N-terminal low-complexity poly-K intrinsically disordered region drives nucleolar targeting through liquid–liquid phase separation, a process negatively regulated by Jmjd6-mediated lysyl hydroxylation of the same poly-K region (PMID:33443146). LIAT1 also directly binds tRNA-Arg in vitro, indicating an additional role in RNA metabolism (PMID:39081859).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2014 High

    Identification of LIAT1 as a direct binding partner and enzymatic activator of Ate1 established the first known regulatory cofactor for N-terminal arginylation, revealing that arginylation is subject to accessory-protein control rather than being solely dictated by Ate1 itself.

    Evidence Co-immunoprecipitation, deletion mapping of a conserved ~30-residue binding region, and reconstituted in vitro arginylation assay with purified components

    PMID:25369936

    Open questions at the time
    • Structural basis of the LIAT1–Ate1 interaction is undefined
    • In vivo substrates whose arginylation depends on LIAT1 have not been identified
    • Mechanism by which LIAT1 stimulates Ate1 catalytic activity (allosteric vs. tRNA delivery) is unknown
  2. 2020 High

    Demonstration that LIAT1's poly-K IDR drives nucleolar localization through liquid–liquid phase separation, and that Jmjd6-mediated lysyl hydroxylation of this region inhibits nucleolar targeting, linked LIAT1 to regulated biomolecular condensate biology and provided the first post-translational control mechanism for LIAT1 localization.

    Evidence Bimolecular fluorescence complementation, immunocytochemistry, domain deletion analysis, and Jmjd6 activity assays in cells

    PMID:33443146

    Open questions at the time
    • Functional consequence of nucleolar LIAT1 condensates (e.g., ribosome biogenesis, rRNA processing) is unknown
    • Whether Jmjd6-mediated regulation of LIAT1 affects Ate1-dependent arginylation has not been tested
    • The precise hydroxylated residues within the poly-K region have not been mapped at single-residue resolution
  3. 2024 Medium

    Discovery that LIAT1 directly binds tRNA-Arg in vitro expanded its functional repertoire beyond protein–protein interaction to RNA binding, raising the possibility that LIAT1 couples tRNA delivery to Ate1-mediated arginylation.

    Evidence In vitro RNA–protein binding assay using recombinant mouse LIAT1 and in vitro–transcribed human tRNA-Arg

    PMID:39081859

    Open questions at the time
    • Binding specificity (tRNA-Arg vs. other tRNAs or RNAs) has not been assessed
    • No mutagenesis to identify the RNA-binding determinant within LIAT1
    • Whether tRNA-Arg binding is relevant to LIAT1's stimulation of Ate1 activity is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central open question is how LIAT1's three activities — Ate1 activation, nucleolar phase separation, and tRNA-Arg binding — are integrated in vivo to regulate N-terminal arginylation and/or nucleolar function.
  • No loss-of-function phenotype for LIAT1 has been reported in any organism
  • Whether LIAT1 acts as a tRNA carrier that delivers Arg-charged tRNA to Ate1 is untested
  • Physiological substrates of the LIAT1–Ate1 axis remain unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005730 nucleolus 1
Partners
ATE1JMJD6

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 LIAT1 (Ligand of Ate1) was identified as a binding partner of the arginyltransferase Ate1, with higher affinity for Ate1 isoforms 1A7A and 1B7A, and a ~30-residue conserved region of LIAT1 was shown to be required for this binding. Co-immunoprecipitation / pulldown; deletion mapping of the conserved ~30-residue region Proceedings of the National Academy of Sciences of the United States of America High 25369936
2014 LIAT1 stimulates the in vitro N-terminal arginylation of a model substrate by Ate1, indicating it functions as a positive regulator of Ate1 enzymatic activity. In vitro arginylation assay with purified components Proceedings of the National Academy of Sciences of the United States of America High 25369936
2020 LIAT1's N-terminal half comprises an intrinsically disordered region (IDR) containing a low-complexity poly-K region that targets LIAT1 to the nucleolus, where it undergoes liquid-liquid phase separation (LLPS). Bimolecular fluorescence complementation, immunocytochemistry, domain deletion analysis Proceedings of the National Academy of Sciences of the United States of America High 33443146
2020 The lysyl-hydroxylase Jumonji Domain Containing 6 (Jmjd6) modifies LIAT1 in a manner dependent on the poly-K region within its IDR, and this modification inhibits LIAT1's nucleolar targeting. Immunocytochemistry, bimolecular fluorescence complementation, Jmjd6 activity assays Proceedings of the National Academy of Sciences of the United States of America Medium 33443146
2024 Human tRNA-Arg directly binds recombinant mouse LIAT1 in vitro, identifying LIAT1 as an RNA-binding protein. In vitro RNA-protein binding assay with recombinant LIAT1 and in vitro-transcribed tRNA-Arg microPublication biology Medium 39081859

Source papers

Stage 0 corpus · 5 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats. Proceedings of the National Academy of Sciences of the United States of America 20 25369936
2020 The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6. Proceedings of the National Academy of Sciences of the United States of America 6 33443146
2024 tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1. microPublication biology 3 39081859
2017 Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study. Human genomics 3 28865488
2025 Erratum: Corrigendum: tRNA Arg binds in vitro TDP-43 RNA recognition motifs and ligand of Ate1 protein LIAT1. microPublication biology 0 39897169