Functional Characterization of Herpesvirus-Activated Noncoding Retrotransposon RNAs

测序技术的进步导致了许多类型的非编码的发现 RNA(NcRNA)在组织动态平衡和疾病病理中发挥重要作用。此外，还有几个 研究已经确定了宿主和病原体编码的ncRNA，其表达模式与 病毒的致病机制、宿主防御和潜伏激活。一类特定的ncRNA已经被 研究表明，在小鼠和人类细胞中，分别调节病毒复制和炎症反应的是 短粒状核素(Sine)，小鼠称为B1-B4，人类称为Alu。这些重复的内容 在健康的体细胞中，元素在表观遗传上是沉默的，但可以被RNA诱导和转录 聚合酶III(Pol3)在各种细胞应激下的表达 ，包括感染了各种DNA 病毒。最近的研究表明，非编码ncRNA的表达可以影响病毒和宿主基因的表达。 Kaposi的近亲小鼠伽玛疱疹病毒MHV68感染过程中的NFκB信号 肉瘤相关疱疹病毒。其他研究已经将正弦蛋白的表达与转录增加联系起来。 干扰素刺激基因(ISG)。鉴于Sine ncRNA在细胞核中积累，并且 细胞质中，它们的基因调控和信号活动是如何在每个隔室中协调的 该领域的基本问题。我们将通过首先构造正弦轨迹激活图来解决这个问题 感染阿尔法或伽马疱疹病毒的细胞，这将用于识别直接编码ncRNA驱动的基因 细胞核中的表达特征及其对病毒复制的影响。然后我们将确定哪些是 细胞质中的天然免疫途径的组成部分参与了对天然转录的氨基酸的感知。 NcRNAs。总而言之，这些结果将为这些“自我”ncRNA如何发挥作用提供新的机械性见解。 影响DNA病毒感染过程中的基因表达格局。

The advancement of sequencing technologies has resulted in the discovery of numerous types of non-coding RNAs (ncRNA) that play important role in both tissue homeostasis and disease pathology. Additionally, several studies have identified host and pathogen-encoded ncRNA whose expression patterns are associated with viral pathogenesis, host defense and activation from latency. One specific class of ncRNA that has been shown to modulate viral replication and inflammatory responses in mouse and human cells, respectively, are the short interspersed nuclear elements (SINEs), termed B1-B4 in mice and Alu in humans. These repetitive elements are epigenetically silenced in healthy somatic cells but can be induced and transcribed by RNA polymerase III (Pol3) upon exposure to various cellular stresses , including infection with a variety of DNA viruses. Recent studies suggest that SINE ncRNA expression can influence viral and host gene expression and NFκB signaling during infection with the murine gammaherpesvirus MHV68, a close relative of Kaposi's sarcoma-associated herpesvirus. Additional studies have linked SINE expression to increased transcription of interferon-stimulated genes (ISG) . Given that SINE ncRNAs accumulate in the nucleus and the cytoplasm, how their gene regulatory and signaling activities are coordinated in each compartment is a fundamental question in the field. We will address this by first constructing a SINE locus activation map in cells infected with alpha or gammaherpesviruses, which will be used to identify direct SINE ncRNA-driven gene expression signatures in the nucleus and their consequences for viral replication. We will then identify which components of the innate immune pathway in the cytoplasm are involved in sensing natively transcribed SINE ncRNAs. Collectively, these results will provide new mechanistic insights into how these “self” ncRNAs function to influence the gene expression landscape during DNA virus infection.