Genome-wide analyses of Epstein-Barr virus reveal conserved RNA structures and a novel stable intronic sequence RNA.
BACKGROUND
Epstein-Barr virus (EBV) is a human herpesvirus implicated in cancer and autoimmune disorders. Little is known concerning the roles of RNA structure in this important human pathogen. This study provides the first comprehensive genome-wide survey of RNA and RNA structure in EBV.


RESULTS
Novel EBV RNAs and RNA structures were identified by computational modeling and RNA-Seq analyses of EBV. Scans of the genomic sequences of four EBV strains (EBV-1, EBV-2, GD1, and GD2) and of the closely related Macacine herpesvirus 4 using the RNAz program discovered 265 regions with high probability of forming conserved RNA structures. Secondary structure models are proposed for these regions based on a combination of free energy minimization and comparative sequence analysis. The analysis of RNA-Seq data uncovered the first observation of a stable intronic sequence RNA (sisRNA) in EBV. The abundance of this sisRNA rivals that of the well-known and highly expressed EBV-encoded non-coding RNAs (EBERs).


CONCLUSIONS
This work identifies regions of the EBV genome likely to generate functional RNAs and RNA structures, provides structural models for these regions, and discusses potential functions suggested by the modeled structures. Enhanced understanding of the EBV transcriptome will guide future experimental analyses of the discovered RNAs and RNA structures.
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Walter N
WN
Moss
Joan A
JA
Steitz
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics; D023281:Genomics; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D020871:RNA Stability; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D022821:RNA Splice Sites; D012367:RNA, Viral