Skip to main content

Properties, functions, and therapeutic prospects of enhancer RNAs

Abstract

The minireview is dedicated to recently described enhancer RNAs (eRNAs), which are products of enhancer transcription. Features and putative functions of eRNAs are considered. The potential of eRNAs as therapeutic targets is discussed.

This is a preview of subscription content, access via your institution.

Abbreviations

eRNA:

enhancer RNA

RNA Pol II:

RNA polymerase II

TSS:

transcription start site

siRNA:

small interfering RNA

References

  1. Cech, T.R. and Steitz, J.A., Cell, 2014, vol. 157, pp. 77–94.

    CAS  Article  PubMed  Google Scholar 

  2. Lam, M.T., Li, W., Rosenfeld, M.G., and Glass, C.K., Trends Biochem. Sci., 2014, vol. 39, pp. 170–182.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Leveille, N., Melo, C.A., and Agami, R., Expert Opin. Biol. Ther., 2015, vol. 15, pp. 723–734.

    CAS  Article  PubMed  Google Scholar 

  4. Natoli, G. and Andrau, J.C., Annu. Rev. Genet., 2012, vol. 46, pp. 1–19.

    CAS  Article  PubMed  Google Scholar 

  5. Murakawa, Y., Yoshihara, M., Kawaji, H., Nishikawa, M., Zayed, H., Suzuki, H., Fantom, C., and Hayashizaki, Y., Trends Genet., 2016, vol. 32, pp. 76–88.

    CAS  Article  PubMed  Google Scholar 

  6. Jiao, A.L. and Slack, F.J., Epigenetics, 2014, vol. 9, pp. 27–36.

    CAS  Article  PubMed  Google Scholar 

  7. Erokhin, M., Vassetzky, Y., Georgiev, P., and Chetverina, D., Cell Mol. Life Sci., 2015, vol. 72, pp. 2361–2375.

    CAS  Article  PubMed  Google Scholar 

  8. Li, W., Notani, D., and Rosenfeld, M.G., Nat. Rev. Genet., 2016, vol. 17, pp. 207–223.

    CAS  Article  PubMed  Google Scholar 

  9. Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., Suzuki, T., et al., Nature, 2014, vol. 507, pp. 455–461.

    CAS  Article  PubMed  Google Scholar 

  10. Young, M.D., Willson, T.A., Wakefield, M.J., Trounson, E., Hilton, D.J., Blewitt, M.E., Oshlack, A., and Majewski, I.J., Nucleic Acids Res., 2011, vol. 39, pp. 7415–7427.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Kuzmich, A.I., Tyulkina, D.V., Vinogradova, T.V., and Sverdlov, E.D., Russ. J. Bioorg. Chem., 2015, vol. 41, pp. 570–577.

    CAS  Article  Google Scholar 

  12. Lai, F., Gardini, A., Zhang, A., and Shiekhattar, R., Nature, 2015, vol. 525, pp. 399–403.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A.Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., et al., Nature, 2013, vol. 498, pp. 516–520.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Djebali, S., Davis, C.A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al., Nature, 2012, vol. 489, pp. 101–108.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Kim, T.K., Hemberg, M., Gray, J.M., Costa, A.M., Bear, D.M., Wu, J., Harmin, D.A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al., Nature, 2010, vol. 465, pp. 182–187.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Pefanis, E., Wang, J., Rothschild, G., Lim, J., Kazadi, D., Sun, J., Federation, A., Chao, J., Elliott, O., Liu, Z.P., et al., Cell, 2015, vol. 161, pp. 774–789.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. De Santa, F., Barozzi, I., Mietton, F., Ghisletti, S., Polletti, S., Tusi, B.K., Muller, H., Ragoussis, J., Wei, C.L., and Natoli, G., PLoS Biol., 2010, vol. 8, p. e1000384.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sanyal, A., Lajoie, B.R., Jain, G., and Dekker, J., Nature, 2012, vol. 489, pp. 109–113.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Cheng, J.H., Pan, D.Z., Tsai, Z.T., and Tsai, H.K., Sci. Rep., 2015, vol. 5, p. 12648.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Shlyueva, D., Stampfel, G., and Stark, A., Nat. Rev. Genet., 2014, vol. 15, pp. 272–286.

    CAS  Article  PubMed  Google Scholar 

  21. Kaikkonen, M.U., Spann, N.J., Heinz, S., Romanoski, C.E., Allison, K.A., Stender, J.D., Chun, H.B., Tough, D.F., Prinjha, R.K., Benner, C., et al., Mol. Cell, 2013, vol. 51, pp. 310–325.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Onodera, C.S., Underwood, J.G., Katzman, S., Jacobs, F., Greenberg, D., Salama, S.R., and Haussler, D., PLoS One, 2012, vol. 7, p. e43511.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Melo, C.A., Drost, J., Wijchers, P.J., van de Werken, H., de Wit, E., Oude Vrielink, J.A., Elkon, R., Melo, S.A., Leveille, N., Kalluri, R., et al., Mol. Cell, 2013, vol. 49, pp. 524–535.

    CAS  Article  PubMed  Google Scholar 

  24. Hsieh, C.L., Fei, T., Chen, Y., Li, T., Gao, Y., Wang, X., Sun, T., Sweeney, C.J., Lee, G.S., Chen, S., et al., Proc. Natl. Acad. Sci. U. S. A, 2014, vol. 111, pp. 7319–7324.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Lam, M.T., Cho, H., Lesch, H.P., Gosselin, D., Heinz, S., Tanaka-Oishi, Y., Benner, C., Kaikkonen, M.U., Kim, A.S., Kosaka, M., et al., Nature, 2013, vol. 498, pp. 511–515.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Mousavi, K., Zare, H., Dell’orso, S., Grontved, L., Gutierrez-Cruz, G., Derfoul, A., Hager, G.L., and Sartorelli, V., Mol. Cell, 2013, vol. 51, pp. 606–617.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Maruyama, A., Mimura, J., and Itoh, K., Nucleic Acids Res., 2014, vol. 42, pp. 13599–13614.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Lai, F., Orom, U.A., Cesaroni, M., Beringer, M., Taatjes, D.J., Blobel, G.A., and Shiekhattar, R., Nature, 2013, vol. 494, pp. 497–501.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Kagey, M.H., Newman, J.J., Bilodeau, S., Zhan, Y., Orlando, D.A., van Berkum, N.L., Ebmeier, C.C., Goossens, J., Rahl, P.B., Levine, S.S., et al., Nature, 2010, vol. 467, pp. 430–435.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Kim, T.K. and Shiekhattar, R., Cell, 2015, vol. 162, pp. 948–959.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Hah, N., Murakami, S., Nagari, A., Danko, C.G., and Kraus, W.L., Genome Res., 2013, vol. 23, pp. 1210–1223.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Schaukowitch, K., Joo, J.Y., Liu, X., Watts, J.K., Martinez, C., and Kim, T.K., Mol. Cell, 2014, vol. 56, pp. 29–42.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Kashkin, K.N. and Sverdlov, E.D., Mol. Biol., 2015, vol. 49, pp. 810–817.

    CAS  Article  Google Scholar 

  34. Arner, E., Daub, C.O., Vitting-Seerup, K., Andersson, R., Lilje, B., Drablos, F., Lennartsson, A., Ronnerblad, M., Hrydziuszko, O., Vitezic, M., et al., Science, 2015, vol. 347, pp. 1010–1014.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Sigova, A.A., Abraham, B.J., Ji, X., Molinie, B., Hannett, N.M., Guo, Y.E., Jangi, M., Giallourakis, C.C., Sharp, P.A., and Young, R.A., Science, 2015, vol. 350, pp. 978–981.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Step, S.E., Lim, H.W., Marinis, J.M., Prokesch, A., Steger, D.J., You, S.H., Won, K.J., and Lazar, M.A., Genes Dev., 2014, vol. 28, pp. 1018–1028.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Wang, D., Garcia-Bassets, I., Benner, C., Li, W., Su, X., Zhou, Y., Qiu, J., Liu, W., Kaikkonen, M.U., Ohgi, K.A., et al., Nature, 2011, vol. 474, pp. 390–394.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Leveille, N., Melo, C.A., Rooijers, K., Diaz-Lagares, A., Melo, S.A., Korkmaz, G., Lopes, R., Akbar., Moqadam F., Maia, A.R., Wijchers, P.J., et al., Nat. Commun., 2015, vol. 6, p. 6520.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Yang, Y., Su, Z., Song, X., Liang, B., Zeng, F., Chang, X., and Huang, D., Sci. Rep., 2016, vol. 6, p. 20961.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Puente, X.S., Bea, S., Valdes-Mas, R., Villamor, N., Gutierrez-Abril, J., Martin-Subero, J.I., Munar, M., Rubio-Perez, C., Jares, P., Aymerich, M., et al., Nature, 2015, vol. 526, pp. 519–524.

    CAS  Article  PubMed  Google Scholar 

  41. Mansour, M.R., Abraham, B.J., Anders, L., Berezovskaya, A., Gutierrez, A., Durbin, A.D., Etchin, J., Lawton, L., Sallan, S.E., Silverman, L.B., et al., Science, 2014, vol. 346, pp. 1373–1377.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Ounzain, S. and Pedrazzini, T., Trends Cardiovasc. Med., 2015, vol. 25, pp. 592–602.

    CAS  Article  PubMed  Google Scholar 

  43. Levine, A.J., Perry, M.E., Chang, A., Silver, A., Dittmer, D., Wu, M., and Welsh, D., Br. J. Cancer, 1994, vol. 69, pp. 409–416.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Kole, R., Krainer, A.R., and Altman, S., Nat. Rev. Drug Discov., 2012, vol. 11, pp. 125–140.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. N. Kashkin.

Additional information

Original Russian Text © K.N. Kashkin, E.D. Sverdlov, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 5, pp. 526–532.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kashkin, K.N., Sverdlov, E.D. Properties, functions, and therapeutic prospects of enhancer RNAs. Russ J Bioorg Chem 42, 473–478 (2016). https://doi.org/10.1134/S1068162016050083

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162016050083

Keywords

  • enhancer
  • enhancer RNA
  • transcription
  • regulation of transcription
  • pancreas
  • tumor
  • cancer