Lee Nara, Moss Walter N, Yario Therese A, Steitz Joan A
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
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.
EBER2是一种由爱泼斯坦-巴尔病毒（EBV）表达的丰富的核非编码RNA。通过染色质RNA分析技术（CHART）探究其可能的染色质定位，结果显示EBER2存在于潜伏性EBV基因组的末端重复序列（TRs）处，与先前鉴定出的B细胞转录因子PAX5的结合位点重叠。EBER2与PAX5相互作用，并且是PAX5定位于TRs所必需的。EBER2敲低在上调最靠近TRs的基因LMP2A/B和LMP1的表达方面模拟了PAX5缺失的表型。敲低EBER2也会降低EBV的裂解复制，这突出了TRs在病毒复制中的重要作用。EBER2-PAX5复合物的募集是由EBER2与TR基因座新生转录本之间的碱基配对介导的。尽管序列差异很大，但在相关的灵长类疱疹病毒CeHV15中，这种相互作用在进化上是保守的。利用与新生RNA的碱基配对来引导相互作用的转录因子到达其DNA靶位点，这是反式作用非编码RNA以前未被描述的功能。
