Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
BMC Genomics. 2013 Aug 9;14:543. doi: 10.1186/1471-2164-14-543.
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.
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).
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.
爱泼斯坦-巴尔病毒（EBV）是一种与癌症和自身免疫性疾病有关的人类疱疹病毒。关于 RNA 结构在这种重要的人类病原体中的作用，人们知之甚少。本研究首次全面调查了 EBV 中的 RNA 和 RNA 结构。
通过 EBV 的计算建模和 RNA-Seq 分析，鉴定出了新型 EBV RNA 和 RNA 结构。使用 RNAz 程序对四种 EBV 株（EBV-1、EBV-2、GD1 和 GD2）和密切相关的猕猴疱疹病毒 4 的基因组序列进行扫描，发现了 265 个具有高概率形成保守 RNA 结构的区域。根据自由能最小化和比较序列分析的组合，为这些区域提出了二级结构模型。对 RNA-Seq 数据的分析首次观察到 EBV 中的稳定内含子序列 RNA（sisRNA）。这种 sisRNA 的丰度可与众所周知的高度表达的 EBV 编码非编码 RNA（EBERs）相媲美。
这项工作确定了 EBV 基因组中可能产生功能性 RNA 和 RNA 结构的区域，为这些区域提供了结构模型，并讨论了模型结构所暗示的潜在功能。对 EBV 转录组的深入了解将指导对发现的 RNA 和 RNA 结构的未来实验分析。
