Affinage

RO60

RNA-binding protein RO60 · UniProt P10155

Length
538 aa
Mass
60.7 kDa
Annotated
2026-06-10
78 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RO60 (TROVE2/SSA2) is a ring-shaped, RNA-binding autoantigen that functions as a noncoding-RNA quality-control factor by capturing structured and misfolded RNAs in its central cavity and partnering with Y RNAs and other effectors to direct their fate (PMID:9872955, PMID:41610850). A cryo-EM and SHAPE-MaP analysis established that Ro60 binds the ends of misfolded ncRNAs in its toroidal cavity while La cradles the Ro60 RNP, the two proteins acting synergistically as a collaborative RNA chaperone machine that unfolds non-native RNA structures (PMID:41610850). The protein's small noncoding Y RNA partners are central to its biology: Ro60 binding promotes Y RNA nuclear export and is required for Y RNA stability and accumulation in vivo (PMID:8608450, PMID:9872955), while reciprocally the Y RNAs are required for Ro60 to reach wild-type protein levels, set its cytoplasmic-versus-nucleolar distribution, and tether it to diverse effector proteins to build specialized RNPs (PMID:32660384). Across bacterial and phage orthologs this tethering function couples Ro60 to ring-shaped 3'-to-5' exoribonucleases such as PNPase, forming double-ringed RYPER-like complexes that act on structured RNA and modulate exoribonuclease activity (PMID:31084369, PMID:40464688). In the cytoplasm Ro60 also engages Ro52/TRIM21 through a weak transient interaction involving residues that overlap its Y RNA-binding surface (PMID:38983778). Ro60 is a principal driver of autoimmune pathology: during apoptosis it becomes surface-exposed on early apoptotic cells in a Y3 RNA-dependent manner (PMID:17286801, PMID:23698747), and the resulting anti-Ro60 immune complexes, carrying Y RNA, activate macrophages through FcγRIIIa-mediated uptake and TLR7/8 ligation, driving NF-κB/STAT1 signaling, TNF-α production, and inflammatory fibrosis (PMID:20089705, PMID:23698747, PMID:26432597). Anti-Ro60 autoantibodies cross-react with Ro60 orthologs in human commensal bacteria, and monocolonization of germ-free mice with such a commensal triggers anti-Ro60 responses and glomerular immune-complex deposition, linking microbial Ro60 to lupus autoimmunity (PMID:29593104).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Establishing why Ro60 matters for Y RNA trafficking, this work showed Ro60 binding directs nuclear export of its Y RNA partner, defining an early functional role in RNP localization.

    Evidence Xenopus oocyte injection of hY1 RNA binding-site mutants with competition studies

    PMID:8608450

    Open questions at the time
    • Mechanism of export-machinery recruitment not defined
    • Done in oocytes, not mammalian somatic cells
  2. 1998 Medium

    Probing whether Ro60 acts beyond Y RNAs, it was found to serve as an ancillary factor enabling La and CNBP binding to a ribosomal-protein mRNA 5'UTR for translational regulation.

    Evidence In vitro RNA binding, UV cross-linking and competition assays in the Xenopus system

    PMID:9710533

    Open questions at the time
    • Functional translational consequence in cells not shown
    • Xenopus ortholog only
  3. 1999 High

    Genetic loss-of-function in C. elegans answered whether Ro60 is needed for Y RNA homeostasis, showing rop-1 disruption collapses Y RNA levels with transgenic rescue.

    Evidence C. elegans rop-1 knockout, Northern blot of CeY RNA, transgenic rescue

    PMID:9872955

    Open questions at the time
    • Mechanism of stabilization (protection vs biogenesis) not resolved
    • Invertebrate system
  4. 2002 Medium

    To connect Ro60 to autoimmunity, live-cell imaging showed Ro60 fills apoptotic blebs and becomes surface-exposed on apoptotic bodies, making it accessible to autoantibodies.

    Evidence EGFP-Ro60 transfection, confocal microscopy, antibody binding to non-fixed apoptotic cells

    PMID:12410795

    Open questions at the time
    • Molecular trigger for surface translocation not identified here
    • Overexpression of tagged construct
  5. 2004 High

    Biochemical reconstitution asked what governs Ro60 protein-protein assembly, identifying Ca2+-dependent intramolecular folding and Ca2+-dependent Ro60-La binding.

    Evidence SPR and Ouchterlony double immunodiffusion with purified Ro60 and ion-specificity controls

    PMID:15234560

    Open questions at the time
    • Physiological relevance of Ca2+ dependence in cells unaddressed
    • Structural basis of Ca2+ binding not defined
  6. 2007 Medium

    Flow cytometry refined the apoptotic-exposure model, showing Ro60 (including its RRM-containing epitope) translocates independently to the surface during early apoptosis, ahead of La.

    Evidence Multi-parameter flow cytometry with monospecific anti-Ro/anti-La IgGs and Annexin V/PI staging

    PMID:17286801

    Open questions at the time
    • Trafficking route not defined
    • Single cell-line system
  7. 2010 High

    This work defined the effector arm of Ro60 autoimmunity, showing Ro60/Y RNA immune complexes activate macrophages via FcγRIIIa uptake and TLR ligation to drive TNF-α and fibrosis.

    Evidence Macrophage ssRNA transfection, anti-CD16a blockade, TLR antagonist/chloroquine, cardiac fibroblast assays, CHB tissue staining

    PMID:20089705

    Open questions at the time
    • Precise TLR (7 vs 8) engagement not fully resolved here
    • In vivo causal demonstration limited
  8. 2010 Medium

    Testing a proposed cellular role, a cell-free system showed Ro60-containing RNPs are dispensable for Y RNA-supported DNA replication, narrowing Ro60's functional scope.

    Evidence Immunodepletion of Ro60 RNPs and recombinant Ro60 add-back in a human cell-free DNA replication assay

    PMID:21060685

    Open questions at the time
    • Negative result; does not exclude indirect roles
    • In vitro extract system
  9. 2013 High

    Structure-function genetics established the molecular requirement for Ro60 surface exposure, showing Y3 RNA binding is obligatory for apoptotic surface translocation and downstream macrophage activation.

    Evidence Ro60-knockout fibroblasts expressing Y-RNA-binding point mutants, mY3/mY1 RNAi, surface flow cytometry, macrophage activation assay

    PMID:23698747

    Open questions at the time
    • Transport machinery carrying the Ro60-Y3 RNP to the surface unknown
    • Mouse fibroblast model
  10. 2015 Medium

    Downstream signaling was dissected, showing Y3 RNA-driven TLR7/8 ligation activates NF-κB and STAT1 and deposits H3K4me2 at the TNF promoter, with hydroxychloroquine selectively blocking part of this output.

    Evidence Immune-complex/hY3 RNA macrophage stimulation, microarray, ChIP-qPCR, hydroxychloroquine treatment

    PMID:26432597

    Open questions at the time
    • Mechanism of signal bifurcation not resolved
    • Single lab
  11. 2018 High

    Addressing the origin of anti-Ro60 autoimmunity, commensal Ro60 orthologs were shown to cross-react with patient antibodies and T cells and to initiate anti-human Ro60 responses with renal immune-complex deposition in monocolonized mice.

    Evidence SLE-serum immunoprecipitation of commensal RNPs, CD4+ T cell clone activation, germ-free mouse monocolonization

    PMID:29593104

    Open questions at the time
    • Causal contribution to human disease onset not established
    • Specific cross-reactive epitopes incompletely mapped
  12. 2019 Medium

    Cross-species biochemistry defined a conserved enzymatic-partnership role, showing bacterial Ro60 enhances 3'-to-5' exoribonuclease degradation of structured RNA with Y RNAs gating cavity access.

    Evidence Biochemical and structural characterization in D. radiodurans (review of primary work)

    PMID:31084369

    Open questions at the time
    • Direct demonstration of RYPER-like degradation in mammalian cells lacking
    • Review-level synthesis
  13. 2020 High

    CRISPR Y RNA knockouts established the reciprocal Ro60-Y RNA dependency, showing Y RNAs are required for Ro60 protein accumulation, set its cytoplasmic/nucleolar distribution, and tether it to effector proteins.

    Evidence CRISPR knockout of mY1/mY3 in mouse ES cells, Western blot, subcellular fractionation, Co-IP, proliferation assays

    PMID:32469055

    Open questions at the time
    • Identity of all mammalian effector proteins not enumerated
    • Mechanism of nucleolar retention unclear
  14. 2020 Medium

    Bacterial reconstitution further defined the RYPER architecture, showing Y RNAs tether Ro60 to ring-shaped PNPase into a double-ringed structured-RNA-degradation machine.

    Evidence Biochemical reconstitution and structural analysis in bacterial systems (review)

    PMID:32660384

    Open questions at the time
    • Conservation of PNPase tethering in human cells not shown
    • Review-level
  15. 2024 Medium

    The cytoplasmic Ro60-Ro52 association was characterized, showing a weak transient complex in which Ro60 docks onto the Ro52 PRY-SPRY domains via residues overlapping its Y RNA-binding surface.

    Evidence Molecular docking, QCM-D, proximity ligation assay, immunofluorescence

    PMID:38983778

    Open questions at the time
    • Functional consequence of Ro60-Ro52 binding undefined
    • Largely computational/biophysical, single lab
  16. 2025 Medium

    High-resolution structures of a phage Ro60 homolog defined the conserved doughnut architecture and confirmed Y RNA-like binding and PNPase attenuation in RYPER-like assemblies.

    Evidence X-ray crystallography at 1.99 Å, cryo-EM of φRo60-Yrl2, PNPase ribonuclease assays

    PMID:40464688

    Open questions at the time
    • Phage ortholog; human structural correspondence inferred
    • Cellular relevance of PNPase attenuation untested
  17. 2026 High

    A cryo-EM/SHAPE-MaP study resolved the central chaperone mechanism, showing Ro60 and La act collaboratively to capture and unfold misfolded ncRNAs, with each protein engaging distinct RNA elements.

    Evidence Cryo-EM of a misfolded ncRNA-Ro60-La complex, SHAPE-MaP, in vitro chaperone assays

    PMID:41610850

    Open questions at the time
    • In-cell substrate repertoire not fully cataloged
    • Link between chaperone activity and downstream RNA decay incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Ro60's RNA quality-control/chaperone activity is mechanistically coupled to its surface translocation and autoimmune effector functions, and which mammalian effector proteins it engages, remains unresolved.
  • No defined mammalian Ro60-exoribonuclease degradation complex
  • Trafficking machinery for apoptotic surface exposure unknown
  • Full catalog of Y RNA-tethered effectors incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005730 nucleolus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 3
Partners
CALRETICULINCNBPHSP70LA/SSBPNPASETRIM21/RO52
Complex memberships
RYPER-like Ro60-Y RNA-exoribonuclease complexRo60-La RNA chaperone complexRo60-Y RNA RNP

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 An intact Ro60 binding site on hY1 RNA is a prerequisite for its nuclear export in Xenopus oocytes, whereas an intact La binding site causes strong nuclear retention. This established that Ro60 binding to Y RNA promotes nuclear export of the Y RNA. Xenopus laevis oocyte injection with hY1 RNA mutants; competition studies with various RNA classes RNA (New York, N.Y.) High 8608450
1998 The Xenopus laevis Ro60 autoantigen functions as an ancillary factor required for binding of La and CNBP proteins to the 5'UTR of ribosomal protein L4 mRNA, facilitating translational regulation. La and CNBP compete for the same factor (Ro60) and bind the 5'UTR in a mutually exclusive manner. CNBP binds as a dimer. In vitro RNA binding assays with purified proteins, competition binding experiments, UV cross-linking, Xenopus oocyte system Journal of molecular biology Medium 9710533
1998 Ro60 ribonucleoprotein is phosphorylated in vivo on tyrosine residues by tyrosine kinase in synchronized HEp-2 cells. Phosphorylation did not alter recognition by anti-Ro antibodies. In vivo 32P metabolic radiolabeling of synchronized HEp-2 cells; immunoprecipitation with monoclonal anti-Ro antibodies; SDS-PAGE and autoradiography Revue du rhumatisme (English ed.) Medium 9540117
1999 In C. elegans, disruption of rop-1 (the Ro60 ortholog) causes a dramatic decrease in levels of the ROP-1-associated Y RNA (CeY RNA), demonstrating that Ro60 is required for Y RNA stability/accumulation in vivo. Transgenic expression of wild-type rop-1 partially rescued CeY RNA levels. C. elegans rop-1 gene disruption (loss-of-function genetics); Northern blot analysis of CeY RNA; transgenic rescue experiment Genetics High 9872955
1999 Ro60 inhibits initiation of transcription by T3 RNA polymerase in a dose-dependent manner in vitro, without affecting elongation or termination, suggesting a role in regulating RNA polymerase III transcript production. In vitro transcription assay using affinity-purified human Ro60 (from spleen extracts) incorporated into T3 RNA polymerase transcription reactions with pTRI-beta-Actin-human DNA template Revue du rhumatisme (English ed.) Low 10418058
1999 Ro60 forms complexes with 5S rRNA together with hY4 and hY5 RNAs, as demonstrated by immunoprecipitation with anti-Ro60 antibodies followed by RT-PCR. Nuclear co-localization of 5S rRNA and Y RNAs was confirmed by in situ hybridization, suggesting Ro60 may participate in ribosome assembly. Immunoprecipitation with anti-Ro60 antibodies; reverse transcription and PCR of precipitated RNA; in situ hybridization Autoimmunity Low 10680747
2000 Immunization with Ro60 peptides induces intramolecular determinant spreading; immune sera depleted of anti-peptide antibody still immunoprecipitated Ro60-associated mY1 and mY3 RNA. Absorption studies demonstrated that a population of induced autoantibodies recognized conformational determinants shared between Ro60, La, SmD, and 70-kDa U1RNP, without sequence homology between these antigens. Antibody absorption/depletion experiments; immunoprecipitation of Ro60-associated RNAs; ELISA inhibition assays in immunized mice Journal of immunology (Baltimore, Md. : 1950) Medium 10843726
2000 During UV-A irradiation of human keratinocytes, enhanced expression and redistribution of Ro60 ribonucleoprotein is caused by Fas-L and Bax gene activation, linking apoptotic signaling pathways to Ro60 antigenic redistribution. UV-A irradiation of human keratinocytes; indirect immunofluorescence; gene expression analysis of Fas-L and Bax Joint bone spine Low 10963075
2002 EGFP-tagged Ro60 is localized both in the nucleus and cytoplasm under normal conditions in human salivary gland (HSG) cells. During early apoptosis, Ro60 localization is maintained (unlike La48 which redistributes to cytoplasm), but all three autoantigens (Ro52, Ro60, La48) fill apoptotic blebs and become surface-exposed on apoptotic bodies, accessible to autoantibodies. Transient transfection of EGFP-tagged constructs; laser confocal microscopy; monoclonal antibody and patient antisera binding to non-fixed apoptotic cells; laser scanning cytometry; TUNEL assay Scandinavian journal of immunology Medium 12410795
2003 Calreticulin binds preferentially to linear B cell epitopes of Ro60 (residues 175-184 and 216-232), and the calreticulin-peptide complex is specifically recognized by anti-Ro60 autoantibodies from SLE/pSS patients. The interaction is favored by heat treatment, divalent cations, and ATP. La/SSB epitopes did not interact with calreticulin. Calreticulin purification from human/pig spleen; ELISA binding of biotinylated Ro60 peptides to calreticulin; serum antibody testing against calreticulin-peptide complexes Clinical and experimental immunology Medium 12974767
2004 Ca2+ ions specifically increase intramolecular and intermolecular protein-protein interactions of Ro60: purified Ro60 forms precipitin lines with Ro60 multiple antigenic peptides (MAPs) only in the presence of Ca2+, and Ro60 binds La only in the presence of Ca2+ as measured by surface plasmon resonance. EDTA/EGTA abolished these interactions. Other divalent ions (Cu2+, Mg2+, Zn2+) did not show the same effect, suggesting Ro60 is a calcium-binding protein whose tertiary structure is Ca2+-dependent. Ouchterlony double immunodiffusion; surface plasmon resonance (SPR) with purified Ro60 and Ro60-MAPs; chelation with EDTA/EGTA; ELISA with SLE sera Molecular immunology High 15234560
2007 Anti-Ro60 antibodies bind specifically to early apoptotic cells (Jurkat) and remain accessible throughout early and late apoptosis, while anti-La binds exclusively to late apoptotic cells and Ro52 is not surface-accessible on either population. The immunodominant internal epitope of Ro60 (containing the RRM) is expressed as an apotope on early apoptotic cells, indicating Ro60 translocates independently to the cell surface during early apoptosis. Multi-parameter flow cytometry with monospecific anti-Ro and anti-La IgGs; early/late apoptosis defined by Annexin V/propidium iodide staining; epitope mapping Clinical and experimental immunology Medium 17286801
2007 Under cell stress (heat and UV irradiation), Ro60 and La proteins are redistributed from the nucleus to the cytoplasm and nucleoplasm, and both proteins undergo self-aggregation. Ro60 and La interact with the cytoskeleton via HSP70 under stress conditions. Indirect immunofluorescence; Western blot; crossed-immunoprecipitation using monoclonal anti-Ro/La or anti-HSP70 linked to CNBr-Sepharose 4B Reumatismo Low 18157285
2010 Ro60-associated single-stranded RNA (ssRNA, specifically noncoding Y RNAs that bind Ro60) activates macrophages via FcγRIIIa (CD16a)-mediated phagocytosis of immune complexes followed by TLR ligation, leading to TNF-α secretion. This TLR-dependent activation drives fibrosis in cardiac fibroblasts. TLR7 immunostaining co-localizes with fibrosis in congenital heart block tissue. Inhibition by IRS661 (TLR7/8 antagonist) and chloroquine confirmed TLR dependence; anti-CD16a antibody confirmed FcγRIIIa dependence. Macrophage transfection with noncoding ssRNA; immune complex formation with anti-Ro60 IgG; ELISA for TNF-α; TLR inhibitor (IRS661) and chloroquine treatment; anti-CD16a blocking; cardiac fibroblast fibrosis assays; TLR7 immunostaining in CHB heart tissue Journal of immunology (Baltimore, Md. : 1950) High 20089705
2010 RNP complexes containing Ro60, La, and hY RNAs (immunoprecipitated from HeLa cytosolic extract) are not required for Y RNA function in chromosomal DNA replication in a human cell-free system. Immunodepletion of Ro60-containing RNPs or addition of excess recombinant Ro60 protein did not inhibit DNA replication in vitro, indicating that Y RNAs can support DNA replication independently of Ro60. Immunoprecipitation of RNP complexes from HeLa cytosolic extract; immunodepletion; human cell-free DNA replication assay; Western blotting and quantitative RT-PCR of RNP composition PloS one Medium 21060685
2013 Y3 RNA binding to Ro60 is required for Ro60 surface translocation during apoptosis. Murine fibroblasts expressing FLAG3-Ro60(H187S) (which cannot bind Y RNA) showed no surface Ro60 during apoptosis, whereas FLAG3-Ro60(K170A R174A) (which binds Y RNA) showed normal surface exposure. RNAi depletion of mY3 RNA (but not mY1 RNA) inhibited surface translocation of Ro60, and overexpression of mY1 RNA did not rescue mY3-depletion. Y RNA was an obligate factor for TLR-dependent macrophage activation by anti-Ro60-opsonized apoptotic fibroblasts. Stable Ro60 knockout murine fibroblasts expressing wild-type or point-mutant FLAG-Ro60; siRNA depletion of mY3 or mY1 RNA; flow cytometry/confocal microscopy for surface Ro60; in vitro macrophage activation assay Journal of immunology (Baltimore, Md. : 1950) High 23698747
2015 TLR7/8 ligation by hY3 RNA (associated with Ro60) activates NF-κB and STAT1 pathways in macrophages, increasing histone H3K4 dimethylation at the kB1 region of the TNF promoter (ChIP-qPCR). Hydroxychloroquine inhibited TLR-dependent NF-κB activation and H3K4me2 but not TNF-α or IFN-α-responsive gene expression, demonstrating bifurcation of TLR downstream signals. Macrophage stimulation with anti-Ro60/Ro60/hY3 RNA immune complexes or hY3 RNA transfection; microarray transcriptomics; ChIP-qPCR for H3K4me2 at TNF promoter kB1 region; hydroxychloroquine treatment Journal of autoimmunity Medium 26432597
2018 Anti-Ro60 autoantibodies cross-react with Ro60 orthologs present in human skin, oral, and gut commensal bacteria. Human anti-Ro60 CD4+ memory T cell clones from lupus patients were activated by Ro60-ortholog-containing bacteria (T cell cross-reactivity). In germ-free mice monocolonized with a Ro60 ortholog-containing gut commensal, anti-human Ro60 T and B cell responses were initiated and glomerular immune complex deposits developed. Immunoprecipitation of commensal Ro60 RNPs by human SLE sera; CD4+ T cell clone activation assays with bacteria; germ-free mouse monocolonization model with immunological and pathological readouts Science translational medicine High 29593104
2019 In bacterial Ro60 orthologs (characterized primarily in Deinococcus radiodurans), Ro60 enhances the ability of 3'-to-5' exoribonucleases to degrade structured RNA during environmental stress. Y RNAs function as regulators that inhibit or permit Ro60 interactions with other proteins and RNAs. Y RNAs tether Ro60 to a ring-shaped exoribonuclease, forming a double-ringed RNP machine for structured RNA degradation, and gate substrate access to the Ro60 cavity. Biochemical characterization in D. radiodurans; structural studies; in vitro RNA degradation assays (reviewed/summarized in Annual Review paper from primary studies) Critical reviews in biochemistry and molecular biology Medium 31084369
2020 Using CRISPR-generated mouse embryonic stem cells lacking one or both murine Y RNAs (mY1 and mY3): (1) Y RNA binding is required for Ro60 to accumulate to wild-type protein levels; (2) Y RNAs regulate subcellular localization of Ro60, with Ro60 reduced in cytoplasm and increased in nucleoli when Y RNAs are absent; (3) Y RNAs tether Ro60 to diverse effector proteins to generate specialized RNPs; (4) cells lacking Y RNAs divide normally, demonstrating Y RNAs are not essential for DNA replication. CRISPR knockout of murine Y RNAs in mouse embryonic stem cells; Western blotting for Ro60 levels; subcellular fractionation; immunoprecipitation for effector protein interactions; cell proliferation assays Nucleic acids research High 32469055
2020 In bacteria, Y RNAs regulate Ro60 by tethering it to a ring-shaped 3'-to-5' exoribonuclease (PNPase), forming a double-ringed RYPER-like complex specialized for structured RNA degradation. Y RNAs also gate substrate access to the Ro60 cavity. A conserved Y RNA domain mimics tRNA structure. Bacterial Ro60 and Y RNA functions have been characterized primarily in D. radiodurans. Biochemical reconstitution, structural analysis, in vitro RNA degradation assays in bacterial systems (D. radiodurans and others) Annual review of microbiology Medium 32660384
2024 Ro60 associates with Ro52 within the cytoplasm, forming a weak transient complex (Ka ≈ 3.7 × 10^6 M−1). Molecular docking and QCM-D show that the toroid-shaped Ro60 interacts with Ro52's Fc receptor region, aligning horizontally within the PRY-SPRY domains of the Ro52 homodimer. Key Ro60 residues K133, W177, and L185 (which are also important for Y RNA binding) are critical for complex stability. Molecular docking; Quartz Crystal Microbalance with Dissipation (QCM-D); Proximity Ligation Assay (PLA); Indirect Immunofluorescence (IIF) EXCLI journal Medium 38983778
2025 Crystal structure of φRo60 (Ro60 homolog from Thermus phage phiLo) determined at 1.99 Å reveals the canonical doughnut-shaped architecture with HEAT repeats and von Willebrand factor A domain. φRo60 binds two Y RNA-like molecules (Yrl1 and Yrl2) with distinct stoichiometries. Cryo-EM of φRo60-Yrl2 reveals a dimeric assembly; key positively charged residues are important for φRo60-Yrl2 interactions. φRo60 and Yrls interact with host PNPase to form tripartite RYPER-like complexes, attenuating PNPase ribonuclease activity. X-ray crystallography (1.99 Å resolution); cryo-electron microscopy; in vitro binding assays; PNPase ribonuclease activity assay Nucleic acids research Medium 40464688
2026 Cryo-EM structure of a misfolded ncRNA complexed with Ro60 and La reveals the molecular mechanism of collaborative RNA chaperoning: Ro60 binds the ends of misfolded ncRNAs in its central cavity, while La cradles the Ro60 RNP with its N-terminal domain binding the RNA 3' end after it exits the Ro60 cavity, and its C-terminal domain destabilizing structures in the misfolded RNA body. SHAPE-MaP analysis showed that La and Ro60 function synergistically to unfold non-native RNA structures, acting as a collaborative RNA chaperone machine for misfolded and aberrant ncRNAs (including ncRNA precursors and those with oligouridine tails). Cryo-electron microscopy structural determination; SHAPE-MaP (selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling); in vitro RNA chaperone assays Cell High 41610850

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Science translational medicine 242 29593104
2014 T cell epitope mimicry between Sjögren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria. Clinical immunology (Orlando, Fla.) 123 24576620
2004 Injection of the 5-HT2C receptor agonist Ro60-0175 into the ventral tegmental area reduces cocaine-induced locomotor activity and cocaine self-administration. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 108 14666118
2002 Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjögren's syndrome. Scandinavian journal of immunology 108 12410795
2007 The 5-HT2C receptor agonist Ro60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine, and contextual cues. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 97 17653111
2010 Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: a novel pathway to autoimmune-associated heart block. Journal of immunology (Baltimore, Md. : 1950) 81 20089705
2019 Ro60 and Y RNAs: structure, functions, and roles in autoimmunity. Critical reviews in biochemistry and molecular biology 77 31084369
1999 Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies. The Journal of experimental medicine 64 9927515
1998 Involvement of the Xenopus laevis Ro60 autoantigen in the alternative interaction of La and CNBP proteins with the 5'UTR of L4 ribosomal protein mRNA. Journal of molecular biology 64 9710533
1996 The interactions with Ro60 and La differentially affect nuclear export of hY1 RNA. RNA (New York, N.Y.) 63 8608450
2012 Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement. Neuropharmacology 58 22342986
2005 Cross-reaction between antibodies to the major epitope of Ro60 kD autoantigen and a homologous peptide of Coxsackie virus 2B protein. Clinical and experimental immunology 50 15958081
2001 Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT(2) agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramine. British journal of pharmacology 45 11399662
1999 The levels of the RoRNP-associated Y RNA are dependent upon the presence of ROP-1, the Caenorhabditis elegans Ro60 protein. Genetics 44 9872955
2002 HLA class II influences the immune response and antibody diversification to Ro60/Sjögren's syndrome-A: heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules. Journal of immunology (Baltimore, Md. : 1950) 43 12023392
2003 Calreticulin binds preferentially with B cell linear epitopes of Ro60 kD autoantigen, enhancing recognition by anti-Ro60 kD autoantibodies. Clinical and experimental immunology 42 12974767
2013 Ro60 requires Y3 RNA for cell surface exposure and inflammation associated with cardiac manifestations of neonatal lupus. Journal of immunology (Baltimore, Md. : 1950) 41 23698747
2014 Global transcript and phenotypic analysis of yeast cells expressing Ssa1, Ssa2, Ssa3 or Ssa4 as sole source of cytosolic Hsp70-Ssa chaperone activity. BMC genomics 39 24628813
2005 The serological pattern of autoantibodies to the Ro52, Ro60, and La48 autoantigens in primary Sjögren's syndrome patients and healthy controls. Scandinavian journal of rheumatology 39 15903026
2007 Different temporal expression of immunodominant Ro60/60 kDa-SSA and La/SSB apotopes. Clinical and experimental immunology 37 17286801
1996 The refolding activity of the yeast heat shock proteins Ssa1 and Ssa2 defines their role in protein translocation. The Journal of cell biology 37 8947547
2000 Ro60 peptides induce antibodies to similar epitopes shared among lupus-related autoantigens. Journal of immunology (Baltimore, Md. : 1950) 33 10843726
2013 Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus. TheScientificWorldJournal 32 24294139
2010 Ribonucleoprotein particles containing non-coding Y RNAs, Ro60, La and nucleolin are not required for Y RNA function in DNA replication. PloS one 32 21060685
2014 Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. Arthritis research & therapy 30 25301447
2013 Ro52- and Ro60-specific B cell pattern in the salivary glands of patients with primary Sjögren's syndrome. Clinical and experimental immunology 30 23574319
2024 Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation. Arthritis & rheumatology (Hoboken, N.J.) 24 38130019
2013 Long-term Ro60 humoral autoimmunity in primary Sjögren's syndrome is maintained by rapid clonal turnover. Clinical immunology (Orlando, Fla.) 23 23644453
2015 Targeting downstream transcription factors and epigenetic modifications following Toll-like receptor 7/8 ligation to forestall tissue injury in anti-Ro60 associated heart block. Journal of autoimmunity 21 26432597
1994 HLA association of anti-Ro60 and anti-Ro52 antibodies in Sjögren's syndrome. Journal of autoimmunity 21 7530962
2022 Antibodies to Both Ro52 and Ro60 for Identifying Sjögren's Syndrome Patients Best Suited for Clinical Trials of Disease-Modifying Therapies. Arthritis care & research 20 33742788
2022 The value of separate detection of anti-Ro52, anti-Ro60 and anti-SSB/La reactivities in relation to diagnosis and phenotypes in primary Sjögren's syndrome. Clinical and experimental rheumatology 17 36200940
2020 Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles. Clinical and experimental immunology 17 32852779
2012 Antagonizing 5-HT₂A receptors with M100907 and stimulating 5-HT₂C receptors with Ro60-0175 blocks cocaine-induced locomotion and zif268 mRNA expression in Sprague-Dawley rats. Behavioural brain research 17 23201361
2006 Post-translational modifications of the major linear epitope 169-190aa of Ro60 kDa autoantigen alter the autoantibody binding. Clinical and experimental immunology 17 16968399
2004 Interaction of calcium and Ro60: increase of antigenicity. Molecular immunology 15 15234560
2024 TAFRO syndrome is associated with anti-SSA/Ro60 antibodies, in contrast to idiopathic castleman disease. Scientific reports 14 38311632
2020 Noncoding Y RNAs regulate the levels, subcellular distribution and protein interactions of their Ro60 autoantigen partner. Nucleic acids research 13 32469055
2020 The Bacterial Ro60 Protein and Its Noncoding Y RNA Regulators. Annual review of microbiology 13 32660384
2018 Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis. Frontiers in immunology 13 30581434
2019 The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate. Molecular biology of the cell 12 31825716
2024 Ro60-Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases. International journal of molecular sciences 10 39062948
2021 Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA. Journal of immunology research 10 33763493
2017 Ro60/SSA levels are increased and promote the progression of pancreatic ductal adenocarcinoma. Biochemical and biophysical research communications 10 29274781
2021 Presence of anti-TIF-1γ, anti-Ro52, anti-SSA/Ro60 and anti-Su/Ago2 antibodies in breast cancer: a cross-sectional study. Immunopharmacology and immunotoxicology 9 33876712
2021 Strong Association of the Myriad Discrete Speckled Nuclear Pattern With Anti-SS-A/Ro60 Antibodies: Consensus Experience of Four International Expert Centers. Frontiers in immunology 9 34675922
2016 Single-cell antibody nanowells: a novel technology in detecting anti-SSA/Ro60- and anti-SSB/La autoantibody-producing cells in peripheral blood of rheumatic disease patients. Arthritis research & therapy 9 27184054
2019 TROVE2 strengthens the anti-inflammatory effect via macrophage polarization by estrogen induction in abdominal aortic aneurysm. Life sciences 6 31863777
2018 New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus erythematosus determined by a combination of QCM-D and DPI. Analytical and bioanalytical chemistry 6 30317445
2018 Ro60 Inhibits Colonic Inflammation and Fibrosis in a Mouse Model of Dextran Sulfate Sodium-Induced Colitis. Immunology letters 6 30395870
2012 Induction of anti-Ro60/anti-La by immunisation with spectrin and induction of anti-spectrin by immunisation with Ro60 and 4-hydroxy-2-nonenal-modified Ro60 immunisation. Clinical and experimental rheumatology 6 22776429
2024 Combination of anti-SSA/Ro60 and anti-dsDNA serotype is predictive of belimumab renal response in patients with lupus nephritis. Lupus science & medicine 5 38806217
2021 Long noncoding RNA distal-less homeobox 2 antisense 1 restrains inflammatory response and apoptosis of periodontal ligament cells by binding with microRNA-330-3p to regulate Ro60, Y RNA binding protein. Archives of oral biology 5 34752991
2006 Search for novel stress-responsive protein components using a yeast mutant lacking two cytosolic Hsp70 genes, SSA1 and SSA2. Molecules and cells 5 16819301
2002 Human Ro60 (SSA2) genomic organization and sequence alterations, examined in cutaneous lupus erythematosus. The British journal of dermatology 5 11903229
2022 IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus. Mediators of inflammation 4 35909659
2016 Characterization of continuous monoclonal antibody epitopes in the N-terminus of Ro60. Biopolymers 4 26506479
2012 Putative sequences on Ro60 three-dimensional structure accessible for 4-hydroxy-2-nonenal (HNE) modification compared to in vitro HNE modification of Ro60 sequences. Molecular immunology 4 22336572
2000 Fas ligand and Bax gene transcription contributes to Ro60 ribonucleoprotein redistribution in UV-A irradiated human keratinocytes. Joint bone spine 4 10963075
1999 The 5S rRNA is associated with Ro60 ribonucleoprotein and is co-precipitated with hYRNAs by anti-Ro antibodies. Autoimmunity 3 10680747
1998 Tyrosine kinase participates in phosphorylation of the Ro60 ribonucleoprotein. Revue du rhumatisme (English ed.) 3 9540117
2025 Hsp70 chaperones, Ssa1 and Ssa2, limit poly(A) binding protein aggregation. Molecular biology of the cell 2 40202836
2024 Clinical features associated with the presence of anti-Ro52 and anti-Ro60 antibodies in Jo-1 antibody-positive anti-synthetase syndrome. Frontiers in immunology 2 38895121
2014 Immunoglobulin-like transcripts 6 (ILT6) polymorphism influences the anti-Ro60/52 autoantibody status in South Indian SLE patients. Lupus 2 24899637
2007 Ro60 and La ribonucleoproteins become self-aggregated by cell stress. Reumatismo 2 18157285
2025 Experimental induction of anti-muscarinic type-3-receptor extracellular loop antibodies by immunization with 4-hydroxy-2-nonenal modified Ro60 and unmodified Ro60. Clinical and experimental immunology 1 39658078
2025 Hsp70 chaperones, Ssa1 and Ssa2, limit poly(A) binding protein aggregation. bioRxiv : the preprint server for biology 1 39896508
2025 Structural and molecular mechanisms of an Ro60 homolog from a Thermus bacteriophage. Nucleic acids research 1 40464688
2023 Effects of HSP70 chaperones Ssa1 and Ssa2 on Ste5 scaffold and the mating mitogen-activated protein kinase (MAPK) pathway in Saccharomyces cerevisiae. PloS one 1 37851593
2022 Discordant Predictions of Extraglandular Involvement in Primary Sjögren's Syndrome According to the Anti-SSA/Ro60 Antibodies Detection Assay in a Cohort Study. Journal of clinical medicine 1 35011983
2019 Effect of coadministration of the GABAB agonist baclofen and the 5-HT2C agonist Ro60-0175 on the expression of amphetamine-induced locomotor sensitization. Experimental brain research 1 30989246
2015 On-Membrane Renaturation of Recombinant Ro60 Autoantigen by Calcium Ions. Methods in molecular biology (Clifton, N.J.) 1 26139273
2011 [Usefulness of anti-SS-A/Ro antibody measurement based on fluorescence enzyme immunoassay with Ro60 and Ro52 antigen]. Rinsho byori. The Japanese journal of clinical pathology 1 21626876
1999 Ro60 ribonucleoprotein inhibits transcription by T3 RNA polymerase in vitro. Revue du rhumatisme (English ed.) 1 10418058
2026 Mechanistic insights into RNA chaperoning by Ro60 and La autoantigens. Cell 0 41610850
2026 International expert consensus recommendations on standardised nomenclature of SSA/Ro (TROVE2/Ro60 and TRIM21/Ro52) autoantibodies in autoimmune diseases. Annals of the rheumatic diseases 0 42135154
2026 Dysregulation of anti-Ro60 B cell autoreactivity in systemic lupus erythematosus. bioRxiv : the preprint server for biology 0 42182241
2024 Unveiling the Ro60-Ro52 complex. EXCLI journal 0 38983778

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