Volume 7 Supplement 1

Proceedings of the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI)

Open Access

Analysis of the miRNA targetome in EBV-infected B cells

  • Rebecca L Skalsky1Email author,
  • David L Corcoran2,
  • Eva Gottwein3,
  • Christopher L Frank1,
  • Markus Hafner4,
  • Jeffrey D Nusbaum4,
  • Regina Feederle5,
  • Henri-Jacques Delecluse5,
  • Micah Luftig1,
  • Thomas Tuschl4,
  • Uwe Ohler2, 6 and
  • Bryan R Cullen1
Infectious Agents and Cancer20127(Suppl 1):O2

DOI: 10.1186/1750-9378-7-S1-O2

Published: 19 April 2012

microRNAs (miRNAs) are ~22 nt, non-coding regulatory RNAs expressed by all metazoans and several viruses. During latent infection, Epstein-Barr virus (EBV) expresses 25 pre-miRNAs and influences the expression of cellular miRNAs, such as miR-155 and miR-21, all of which potentially have roles in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of viral miRNAs in viral pathogenesis and/or oncogenesis is not well defined. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) [1] combined with high-throughput sequencing and computational analysis [2], we interrogated the miRNA targetome in EBV-infected B cells. We identified miRNA binding sites in over 5,700 cellular 3’ untranslated regions (UTRs), 25% of which contained sites for EBV miRNAs. miRNA binding sites were also identified at a lower frequency in coding regions. Our results reveal that EBV miRNAs predominantly target host cellular transcripts, thereby reshaping the host environment. Furthermore, viral miRNA targets are involved in multiple biological processes that are directly relevant to EBV infection, including modulation of immune responses, cell proliferation, and cell survival. Finally, we identified a number of viral transcripts that contained conserved binding sites for cellular miRNAs, including members of the myc-regulated miR-17/92 cluster. This comprehensive survey of the miRNA targetome in EBV-infected B cells is a positive step towards identifying novel therapeutic targets for EBV-associated malignancies.

Authors’ Affiliations

(1)
Department of Molecular Genetics and Microbiology, Duke University
(2)
Duke Institute for Genome Sciences and Policy, Duke University
(3)
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine
(4)
Laboratory of RNA Molecular Biology, The Rockefeller University
(5)
German Cancer Research Center, Department of Virus-associated Tumours
(6)
Department of Biostatistics and Bioinformatics, Duke University

References

  1. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M, Jungkamp AC, Munschauer M: et al., Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell. 2010, 141 (1): 129-41. 10.1016/j.cell.2010.03.009.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Corcoran DL, Georgiev S, Mukherjee N, Gottwein E, Skalsky RL, Keene JD, Ohler U: PARalyzer: Definition of RNA binding sites from PAR-CLIP short-read sequence data. Genome Biol. 2011, 12 (8): R79-10.1186/gb-2011-12-8-r79.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Skalsky et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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