EBV noncoding RNA binds nascent RNA to drive host PAX5 to viral DNA

Cell. 2015 Feb 12;160(4):607-618. doi: 10.1016/j.cell.2015.01.015. Epub 2015 Feb 5.


EBER2 is an abundant nuclear noncoding RNA expressed by the Epstein-Barr virus (EBV). Probing its possible chromatin localization by CHART revealed EBER2's presence at the terminal repeats (TRs) of the latent EBV genome, overlapping previously identified binding sites for the B cell transcription factor PAX5. EBER2 interacts with PAX5 and is required for the localization of PAX5 to the TRs. EBER2 knockdown phenocopies PAX5 depletion in upregulating the expression of LMP2A/B and LMP1, genes nearest the TRs. Knockdown of EBER2 also decreases EBV lytic replication, underscoring the essential role of the TRs in viral replication. Recruitment of the EBER2-PAX5 complex is mediated by base-pairing between EBER2 and nascent transcripts from the TR locus. The interaction is evolutionarily conserved in the related primate herpesvirus CeHV15 despite great sequence divergence. Using base-pairing with nascent RNA to guide an interacting transcription factor to its DNA target site is a previously undescribed function for a trans-acting noncoding RNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Electrophoretic Mobility Shift Assay
  • Gene Knockdown Techniques
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • PAX5 Transcription Factor / metabolism*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Tandem Repeat Sequences
  • Viral Matrix Proteins / genetics
  • Virus Replication


  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr virus encoded RNA 2
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • RNA, Viral
  • Viral Matrix Proteins

Associated data

  • SRA/SRR1640963