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Noncanonical Functions of the Human Ribosomal Repeat

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Ribosomal genes encode ribosomal RNA (rRNA), which is an integral part of ribosomes. The main function of ribosomal genes in the cell is the synthesis of rRNA. However, ribosomal genes can also perform other functions in the body. It was found that DNA of ribosomal genes (rDNA) is an active biomolecule, which can be attributed to the family of DAMPs (danger-associated molecular patterns). Three unusual characteristics of rDNA confer to it the properties of a DAMP molecule: (1) high content of unmethylated CpG motifs—ligands of DNA sensing TLR9; (2) low oxidation potential; and (3) resistance to fragmentation under the accumulation of single-strand breaks in rDNA chains. Owing to these properties, rDNA fragments are accumulated as a part of circulating extracellular DNA and stimulate the TLR9–MyD88–NF-kB signaling pathway in various cells of the body. Oxidized rDNA permeates into the cells, where it can stimulate other DNA sensors (AIM2, RIG1, STING). Extracellular oxidized rDNA reaches the structures of the nucleolus and affects the level of rRNA in the cell. The body defends itself against the excess of extracellular rDNA by producing antibodies to rDNA, which form much stronger complexes with rDNA than common antibodies to double-stranded DNA. It is reasonable to further study extracellular rDNA as a potential target in the treatment of autoimmune, oncological, and cardiovascular diseases.

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This work was financially supported by the Russian Foundation for Basic Research (project no. 17-29-06017ofi_m) and within the State Task of the Ministry of Education and Science of the Russian Federation.

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Correspondence to N. N. Veiko or S. V. Kostyuk.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Ershova, E.S., Konkova, M.S., Malinovskaya, E.M. et al. Noncanonical Functions of the Human Ribosomal Repeat. Russ J Genet 56, 30–40 (2020).

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  • DAMPs
  • human ribosomal genes
  • rDNA
  • TLR9
  • cfDNA
  • oxidized DNA