Friday, August 8, 2025
No menu items!
HomeNatureRNA N-glycosylation enables immune evasion and homeostatic efferocytosis

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis

  • Varki, A. et al. Essentials of Glycobiology 3rd edn (Cold Spring Harbor Laboratory Press, 2015).

  • Flynn, R. A. et al. Small RNAs are modified with N-glycans and displayed on the surface of living cells. Cell 184, 3109–3124 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xie, Y. et al. The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA. Cell 187, 5228–5237.e12 (2024).

  • Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732–738 (2001).

    ADS 
    PubMed 

    Google Scholar
     

  • Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529–1531 (2004).

    ADS 
    PubMed 

    Google Scholar
     

  • Heil, F. et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303, 1526–1529 (2004).

    ADS 
    PubMed 

    Google Scholar
     

  • Greulich, W. et al. TLR8 is a sensor of RNase T2 degradation products. Cell 179, 1264–1275 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Asami, J. & Shimizu, T. Structural and functional understanding of the Toll-like receptors. Protein Sci. 30, 761–772 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yoneyama, M. et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5, 730–737 (2004).

    PubMed 

    Google Scholar
     

  • Kato, H. et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 205, 1601–1610 (2008).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sato, M. et al. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Lett. 441, 106–110 (1998).

    ADS 
    PubMed 

    Google Scholar
     

  • Juang, Y. T. et al. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl Acad. Sci. USA 95, 9837–9842 (1998).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, Y. et al. TLR7 promotes skin inflammation via activating NFκB-mTORC1 axis in rosacea. PeerJ 11, e15976 (2023).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nainytė, M., Amatov, T. & Carell, T. Synthesis of an acp. Chem. Commun. 55, 12216–12218 (2019).


    Google Scholar
     

  • Ma, Y. et al. Spatial imaging of glycoRNA in single cells with ARPLA. Nat. Biotechnol. 42, 608–616 (2023).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ren, Z. et al. Enzyme-mediated proximity labeling identifies small RNAs in the endoplasmic reticulum lumen. Biochemistry 62, 1844–1848 (2023).

    PubMed 

    Google Scholar
     

  • Arandjelovic, S. & Ravichandran, K. S. Phagocytosis of apoptotic cells in homeostasis. Nat. Immunol. 16, 907–917 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kawano, M. & Nagata, S. Efferocytosis and autoimmune disease. Int. Immunol. 30, 551–558 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xie, Y. et al. Development and application of GlycanDIA workflow for glycomic analysis. Preprint at bioRxiv https://doi.org/10.1101/2024.03.12.584702 (2024).

  • Perr, J. et al. RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry. Cell https://doi.org/10.1016/j.cell.2025.01.040 (2025).

    PubMed 

    Google Scholar
     

  • Kawai, T., Ikegawa, M., Ori, D. & Akira, S. Decoding Toll-like receptors: recent insights and perspectives in innate immunity. Immunity 57, 649–673 (2024).

    PubMed 

    Google Scholar
     

  • Fisch, D. et al. Molecular definition of the endogenous Toll-like receptor signalling pathways. Nature 631, 635–644 (2024).

    PubMed 

    Google Scholar
     

  • Godoy, P. M. et al. Large differences in small RNA composition between human biofluids. Cell Rep. 25, 1346–1358 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Srinivasan, S. et al. Small RNA sequencing across diverse biofluids identifies optimal methods for exRNA isolation. Cell 177, 446–462 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brown, G. J. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349–356 (2022).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Satterthwaite, A. B. TLR7 signaling in lupus B cells: new insights into synergizing factors and downstream signals. Curr. Rheumatol. Rep. 23, 80 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dorrity, T. J. et al. Long 3’UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation. Sci. Immunol. 8, eadg2979 (2023).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Maharana, S. et al. SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA. Mol. Cell 82, 3712–3728 (2022).

    PubMed 

    Google Scholar
     

  • Davis, P., Cunnington, P. & Hughes, G. Double-stranded RNA antibodies in systemic lupus erythematosus. Ann. Rheum. Disease. 34, 239 (1975).


    Google Scholar
     

  • Boada-Romero, E., Martinez, J., Heckmann, B. L. & Green, D. R. The clearance of dead cells by efferocytosis. Nat. Rev. Mol. Cell Biol. 21, 398–414 (2020).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, S. J. et al. Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells. Exp. Mol. Med. 46, e76 (2014).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elliott, M. R. & Ravichandran, K. S. The dynamics of apoptotic cell clearance. Dev. Cell 38, 147–160 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piva, T. J., Davern, C. M., Hall, P. M., Winterford, C. M. & Ellem, K. A. O. Increased activity of cell surface peptidases in HeLa cells undergoing UV-induced apoptosis is not mediated by caspase 3. Int. J. Mol. Sci. 13, 2650–2675 (2012).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takakura, M., Ishiguro, K., Akichika, S., Miyauchi, K. & Suzuki, T. Biogenesis and functions of aminocarboxypropyluridine in tRNA. Nat. Commun. 10, 5542 (2019).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, N. et al. Cell surface RNAs control neutrophil recruitment. Cell 187, 846–860 (2024).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, B. et al. Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways. Sci. Signal. 9, ra70 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sakaniwa, K. et al. TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction. Nat. Commun. 14, 164 (2023).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leonard, J. N. et al. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc. Natl Acad. Sci. USA 105, 258–263 (2008).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barrat, F. J., Elkon, K. B. & Fitzgerald, K. A. Importance of nucleic acid recognition in inflammation and autoimmunity. Annu. Rev. Med. 67, 323–336 (2016).

    PubMed 

    Google Scholar
     

  • Koffler, D., Agnello, V. & Kimkel, H. G. Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am. J. Pathol. 74, 109–124 (1974).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jenks, S. A. et al. B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus. Ann. Rheum. Dis. 80, 1190–1200 (2021).

    PubMed 

    Google Scholar
     

  • Franceschini, F. & Cavazzana, I. Anti-Ro/SSA and La/SSB antibodies. Autoimmunity 38, 55–63 (2005).

    PubMed 

    Google Scholar
     

  • Migliorini, P., Baldini, C., Rocchi, V. & Bombardieri, S. Anti-Sm and anti-RNP antibodies. Autoimmunity 38, 47–54 (2005).

    PubMed 

    Google Scholar
     

  • Ah Kioon, M. D. et al. Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity. Immunol. Rev. 323, 241–256 (2024)

    PubMed 

    Google Scholar
     

  • Barrat, F. J. & Su, L. A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection. J. Exp. Med. 216, 1974–1985 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reizis, B. Plasmacytoid dendritic cells: development, regulation, and function. Immunity 50, 37–50 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuriakose, J. et al. Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis. J. Clin. Invest. 129, 2251–2265 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Du, Y. et al. Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation. J. Exp. Med. 219, e20212142 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roberts, Z. J. et al. The chemotherapeutic agent DMXAA potently and specifically activates the TBK1-IRF-3 signaling axis. J. Exp. Med. 204, 1559–1569 (2007).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907–915 (2019)

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, giab008 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pertea, M. et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33, 290–295 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Frazee, A. C. et al. Ballgown bridges the gap between transcriptome assembly and expression analysis. Nat. Biotechnol. 33, 243–246 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Krämer, A., Green, J., Pollard, J. & Tugendreich, S. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30, 523–530 (2014).

    PubMed 

    Google Scholar
     

  • RELATED ARTICLES

    Most Popular

    Recent Comments