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Circular RNAs of human blood cells, plasma, and plasma subfractions


Circular RNAs (circRNAs) are a novel class of regulatory noncoding RNAs with the closed structure of a phosphate–ribose chain. Here, we searched for the characteristic sequences of exon–exon junctions of circular RNAs in high-throughput sequencing data of RNA from human blood cells, plasma, and plasma subfractions. Eighty-eight characteristic junctions of circular RNAs’ exons were identified, eight of which are related to fragments of previously unannotated novel circular human transcripts. The set of 88 circular RNAs identified in human blood was enriched with transcripts of genes encoding transcription factors and proteins involved in biogenesis and transport of membrane vesicles. RT-PCR analysis of circular RNA content in human blood plasma subfractions revealed full-length circular transcripts mostly in fractions of blood plasma membrane particles, such as microvesicles and exosomes. Our results and previously published data suggest that extracellular circular RNAs may be regulators of fundamental cellular processes. The results can be used for the development of novel methods of low invasive diagnostics of human diseases.

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circular RNA


competitive endogenous RNAs


exon–intron circular RNAs


splice acceptor site


splice donor site


non-small cell lung cancer


  1. Zhang, X.O., Wang, H.B., Zhang, Y., Lu, X., Chen, L.L., and Yang, L., Cell, 2014, vol. 159, no. 1, pp. 134–147.

    CAS  Article  PubMed  Google Scholar 

  2. Ashwal-Fluss, R., Meyer, M., Pamudurti, N.R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., and Kadener, S., Mol. Cell, 2014, vol. 56, no. 1, pp. 55–66.

    CAS  Article  PubMed  Google Scholar 

  3. Conn, S.J., Pillman, K.A., Toubia, J., Conn, V.M., Salmanidis, M., Phillips, C.A., Roslan, S., Schreiber, A.W., Gregory, P.A., and Goodall, G.J., Cell, 2015, vol. 160, no. 6, pp. 1125–1134.

    CAS  Article  PubMed  Google Scholar 

  4. Ebbesen, K.K., Kjems, J., and Hansen, T.B., Biochim. Biophys. Acta (BBA)—Gene Regulatory Mechanisms, 2016, vol. 1859, no. 1, pp. 163–168.

    CAS  Article  Google Scholar 

  5. Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S.D., Gregersen, L.H., Munschauer, M., and Loewer, A., Nature, 2013, vol. 495, pp. 333–338.

    CAS  Article  PubMed  Google Scholar 

  6. Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., Zhong, G., Yu, B., Hu, W., Dai, L., and Zhu, P., Nat. Struct. Mol. Biol., 2015, vol. 22, no. 3, pp. 256–264.

    CAS  Article  PubMed  Google Scholar 

  7. Jeck, W.R., Sorrentino, J.A., Wang, K., Slevin, M.K., Burd, C.E., Liu, J., Marzluff, W.F., and Sharpless, N.E., RNA, 2013, vol. 19, no. 2, pp. 141–157.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., Chen, D., Gu, J., He, X., and Huang, S., Cell Res., 2015, vol. 25, no. 8, pp. 981–984.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Guo, J.U., Agarwal, V., Guo, H., and Bartel, D.P., Genome Biol., 2014, vol. 15, no. 7, p. 409.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang, Y., Zhang, X.O., Chen, T., Xiang, J.F., Yin, Q.F., Xing, Y.H., Zhu, S., Yang, L., and Chen, L.L., Mol. Cell, 2013, vol. 51, no. 6, pp. 792–806.

    CAS  Article  PubMed  Google Scholar 

  11. Hansen, T.B., Jensen, T.I., Clausen, B.H., Bramsen, J.B., Finsen, B., Damgaard, C.K., and Kjems, J., Nature, 2013, vol. 495, no. 7441, pp. 384–388.

    CAS  Article  PubMed  Google Scholar 

  12. Salmena, L., Poliseno, L., Tay, Y., Kats, L., and Pandolfi, P.P., Cell, 2011, vol. 146, no. 3, pp. 353–358.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Qu, S., Yang, X., Li, X., Wang, J., Gao, Y., Shang, R., Sun, W., Dou, K., and Li, H., Cancer Lett., 2015, vol. 365, no. 2, pp. 141–148.

    CAS  Article  PubMed  Google Scholar 

  14. Salzman, J., Chen, R.E., Olsen, M.N., Wang, P.L., and Brown, P.O., PLoS Genet., 2013, vol. 9, no. 9, p. e1003777.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Xuan, L., Qu, L., Zhou, H., Wang, P., Yu, H., Wu, T., Wang, X., Li, Q., Tian, L., Liu, M., and Sun, Y., Am. J. Translat. Res., vol. 8, no. 2, p. 932.

  16. Qu, S., Song, W., Yang, X., Wang, J., Zhang, R., Zhang, Z., Zhang, H., and Li, H., Genomics Data, 2015, vol. 5, pp. 385–387.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chen, Y., Li, C., Tan, C., and Liu, X., J. Med. Genet., 2016, vol. 53, no. 6, pp. 359–365.

    Article  PubMed  Google Scholar 

  18. Bahn, J.H., Zhang, Q., Li, F., Chan, T.M., Lin, X., Kim, Y., Wong, D.T., and Xiao, X., Clin. Chem., 2015, vol. 61, no. 1, pp. 221–230.

    CAS  Article  PubMed  Google Scholar 

  19. Koh, W., Pan, W., Gawad, C., Fan, H.C., Kerchner, G.A., Wyss-Coray, T., Blumenfeld, Y.J., El-Sayed, Y.Y., and Quake, S.R., Proc. Natl. Acad. Sci. U. S. A., 2014, vol. 111, no. 20, pp. 7361–7366.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Yáñez-Mó, M., Siljander, P.R., Andreu, Z., Zavec, A.B., Borràs, F.E., Buzas, E.I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., and Colás, E., J. Extracell. Vesicles, 2015, vol. 4 Article ID 27066. doi: 10.3402/jev.v4.27066

    Google Scholar 

  21. Turchinovich, A., Weiz, L., Langheinz, A., and Burwinkel, B., Nucleic Acids Res., vol. 39, no. 16, pp. 7223–7233.

  22. Muller, Ls., Mitsuhashi, M., Simms, P., Gooding, W.E., and Whiteside, T.L., Sci. Rep., 2016, vol. 6.

    Google Scholar 

  23. Glazar, P., Papavasileiou, P., and Rajewsky, N., RNA, 2014, vol. 11, no. 20, pp. 1666–1670.

    Article  Google Scholar 

  24. Memczak, S., Papavasileiou, P., Peters, O., and Rajewsky, N., PLoS ONE, 2015, vol. 10, no. 10, p. e0141214.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chomczynski, P. and Sacchi, N., Nat. Protoc., 2006, vol. 1, pp. 581–585.

    CAS  Article  PubMed  Google Scholar 

  26. Semenov, D.V., Baryakin, D.N., Brenner, E.V., Kurilshikov, A.M., Vasiliev, G.V., Bryzgalov, L.A., Chikova, E.D., Filippova, J.A., Kuligina, E.V., and Richter, V.A., Expert Opin. Biol. Ther., 2012, vol. 12, pp. 43–51.

    Article  Google Scholar 

  27. master/

  28. Langmead, B., Trapnell, C., Pop, M., and Salzberg, S.L., Genome Biol., 2009, vol. 10, no. 3. Article ID R25. doi: 10.1186/gb-2009-10-3-r25

    Google Scholar 

  29. Salzman, J., Gawad, C., Wang, P.L., Lacayo, N., and Brown, P.O., PLoS ONE, 2012, vol. 7, no. 2, e30733.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., and Herzog, M., Mol. Cell, 2015, vol. 58, no. 5, pp. 870–885.

    CAS  Article  PubMed  Google Scholar 

  31. Mi, H., Poudel, S., Muruganujan, A., Casagrande, J.T., and Thomas, P.D., Nucleic Acids Res., 2016, vol. 44, no. D1, pp. D336–D342.

    Article  PubMed  Google Scholar 

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Correspondence to A. V. Savelyeva.

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The paper is based on the materials of “Chemical Biology 2016” conference; Novosibirsk, July 24–29 2016.

Original Russian Text © A.V. Savelyeva, D.N. Bariakin, E.V. Kuligina, V.V. Morozov, V.A. Richter, D.V. Semenov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 2, pp. 133–145.

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Savelyeva, A.V., Bariakin, D.N., Kuligina, E.V. et al. Circular RNAs of human blood cells, plasma, and plasma subfractions. Russ J Bioorg Chem 43, 115–125 (2017).

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  • circular RNA
  • exosomes
  • extracellular RNA
  • human blood plasma RNA
  • long non-coding RNA
  • microvesicles