title: EBV noncoding RNA binds nascent RNA to drive host PAX5 to viral DNA.
abstract: 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.
authors: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors: Nara
authors: N
authors: Lee
authors: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors: Walter N
authors: WN
authors: Moss
authors: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors: Therese A
authors: TA
authors: Yario
authors: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.
authors: Joan A
authors: JA
authors: Steitz
mesh_terms: D001483:Base Sequence; D024202:Electrophoretic Mobility Shift Assay; D055785:Gene Knockdown Techniques; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D051757:PAX5 Transcription Factor / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020080:Tandem Repeat Sequences; D014763:Viral Matrix Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C106732:Epstein-Barr virus encoded RNA 2; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D012367:RNA, Viral; D014763:Viral Matrix Proteins