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de Julián Ortiz, J. V., Pallardó, F. V., González-Cabo, P., Blasco, S., & Gimenez-Romero, D. The Ro60-Ro52 Complex as a New Player in Intracellular Humoral Immunity. Journal of Mosaic of Autoimmunity. 2025. doi: Retrieved from https://www.sciltp.com/journals/jmai/article/view/649
Volume 1, Issue 1, 2025
Copyright (c) 2025 by the authors.
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This work is licensed under a Creative Commons Attribution 4.0 International License.

Short Communication

The Ro60-Ro52 Complex as a New Player in Intracellular Humoral Immunity

Jesus Vicente de Julián-Ortiz 1,*, Federico V. Pallardó 2,3, Pilar González-Cabo 2,3, Salvador Blasco 4 and David Gimenez-Romero 5,*

1 Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés 0, 46100 Valencia, Spain

2 Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, 46010 Valencia, Spain

3 CIBER Rare Diseases (CIBERER), 46010 Valencia, Spain

4 Department of Inorganic Chemistry, Faculty of Chemistry, University of Valencia, C/Doctor Moliner 50, 46100 Burjassot, Spain

5 Department of Physical Chemistry, Faculty of Chemistry, University of Valencia, C/Doctor Moliner 50, 46100 Burjassot, Spain

* Correspondence: jesus.julian@uv.es (J.V.d.J.-O.); david.gimenez-romero@uv.es (D.G.-R.)

Received: 10 December 2024; Revised: 25 December 2024; Accepted: 14 January 2025; Published: 16 January 2025

Abstract: The Ro/SSA antigen complex contains Ro60 (TROVE2), Ro52 (TRIM21), and Y-RNA molecules that have recently emerged as the cornerstone of intracellular immunity and are thought to be the main target of autoantibodies in systemic autoimmune diseases. For decades, the precise nature of the Ro60-Ro52 interaction has been a matter of controversy. We have recently shown that the Ro60-Ro52 complex is transient and dynamic under physiological conditions. These results not only improve our understanding of Ro antigen biology but also highlight the possibility of targeted modulation approaches for autoimmune diseases. This communication explores a fascinating and largely unexplored aspect of intracellular humoral immunity through the Ro60-Ro52 complex, aiming to deepen our understanding of this pivotal interaction and its implications for cellular processes and disease.

Keywords:

intracellular humoral immunity Ro60-Ro52 complex Ro52/TRIM21 Ro60/TROVE2 proteasomal degradation RNA quality control ubiquitin E3 ligase systemic autoimmune diseases

References

  1. Foss, S.; Bottermann, M.; Jonsson, A.; et al. TRIM21-From Intracellular Immunity to Therapy. Front. Immunol. 2019, 10, 3049.
  2. Mallery, D.; McEwan, W.; Bidgood, S.; et al. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc. Natl. Acad. Sci. USA 2010, 107, 19985–19990.
  3. Ozato, K.; Shin, D.; Chang, T.; et al. TRIM family proteins and their emerging roles in innate immunity. Nat. Rev. Immunol. 2008, 8, 849–860.
  4. Fletcher, A.; Mallery, D.; Watkinson, R.; et al. Sequential ubiquitination and deubiquitination enzymes synchronize the dual sensor and effector functions of TRIM21. Proc. Natl. Acad. Sci. USA 2015, 112, 10014–10019.
  5. Lerner, M.R.; Boyle, J.A.; Hardin, J.A.; et al. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science 1981, 211, 400–402.
  6. Benchetrit, E.; Chan, E.K.; Sullivan, K.F.; et al. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J. Exp. Med. 1988, 167, 1560–1571.
  7. Wolin, S.; Steitz, J. The Ro small cytoplasmic ribonucleoproteins: Identification of the antigenic protein and its binding site on the Ro RNAs. Proc. Natl. Acad. Sci. USA 1984, 81, 1996–2000.
  8. Boccitto, M.; Wolin, S. Ro60 and Y RNAs: Structure, functions, and roles in autoimmunity. Crit. Rev. Biochem. Mol. Biol. 2019, 54, 133–152.
  9. Boire, G.; Gendron, M.; Monast, N.; et al. Purification of antigenically intact Ro ribonucleoproteins; biochemical and immunological evidence that the 52-kD protein is not a Ro protein. Clin. Exp. Immunol. 1995, 100, 489–498.
  10. Kelekar, A.; Saitta, M.; Keene, J. Molecular composition of Ro small ribonucleoprotein complexes in human cells. Intracellular localization of the 60-and 52-kD proteins. J. Clin. Investig. 1994, 93, 1637–1644.
  11. Rodríguez, L.; de Julián-Ortiz, J.V.; de la Rúa, F.; et al. Unveiling the Ro60-Ro52 Complex. EXCLI J. 2024, 23, 888–903.
  12. Slobbe, R.L.; Pluk, W.; van Venrooij, W.J.; et al. Ro ribonucleoprotein assembly in vitro: Identification of RNA-protein and protein-protein interactions. J. Mol. Biol. 1992, 227, 361–366.
  13. Keech, C.L.; Gordon, T.P.; McCluskey, J. The immune response to 52-KDA ro and 60-KDA RO is linked in experimental autoimmunity. J. Immunol. 1996, 157, 3694–3699.
  14. Tseng, C.E.; Chan, E.K.; Miranda, E.; et al. The 52-KD protein as a target of intermolecular spreading of the immune response to components of the SS-A/ro-ss-b/la complex. Arthritis Rheum. 1997, 40, 5.
  15. Sim, S.; Wolin, S. Emerging roles for the Ro 60-kDa autoantigen in noncoding RNA metabolism. Wiley Interdiscip. Rev. RNA 2011, 2, 686–699.
  16. Chen, X.; Taylor, D.; Fowler, C.; et al. An RNA Degradation Machine Sculpted by Ro Autoantigen and Noncoding RNA. Cell 2013, 153, 166–177.
  17. Chen, X.; Wurtmann, E.; Van Batavia, J.; et al. An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans. Genes Dev. 2007, 21, 1328–1339.
  18. Jones, E.L.; Laidlaw, S.M.; Dustin, L.B. TRIM21/Ro52–Roles in Innate Immunity and Autoimmune Disease. Front. Immunol. 2021, 12, 738473.
  19. Abraham, M.J.; Murtola, T.; Schulz, R.; et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 2015, 1, 19–25.
  20. Bjelkmar, P.; Larsson, P.; Cuendet, M.A.; et al. Implementation of the CHARMM force field in GROMACS: Analysis of protein stability effects from correction maps, virtual interaction sites, and water models. J. Chem. Theory Comput. 2010, 6, 459–466.
  21. Hess, B.; Bekker, H.; Berendsen, H.J.C.; et al. LINCS: A Linear Constraint Solver for molecular simulations. J. Comput. Chem. 1997, 18, 1463–1472.
  22. Miyamoto, S.; Kollman, P.A. SETTLE: An Analytical Version of the SHAKE and RATTLE Algorithms for Rigid Water Models. J. Comput. Chem. 1992, 13, 952–962.
  23. Essmann, U.; Perera, L.; Berkowitz, M.L.; et al. A smooth particle mesh Ewald method. J. Chem. Phys. 1995, 103, 8577–8592.
  24. Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 2007, 126, 014101.
  25. Bernetti, M.; Bussi, G. Pressure control using stochastic cell rescaling. J. Chem. Phys. 2020, 153, 114107.
  26. Hub, J.S.; de Groot, B.L.; van der Spoel, D. g_wham-A free weighted histogram analysis implementation including robust error and autocorrelation estimates. J. Chem. Theory Comput. 2010, 6, 3713–3720.
  27. Available online: https://www.uv.es/jejuor/SLE/Umbrella%20Sampling%20Pull.mp4 (accessed on 14 January 2025).