非正规的circRNA生物发生是由α和gamma疹病毒驱动的
Sarah E Dremel1,2, Vishal N Koparde3,4, Jesse H Arbuckle5
1HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, 20892, USA.
The EMBO journal
|March 3, 2025
概括
疹病毒在感染过程中产生独特的圆形RNA (circRNA),其中一些对正常拼接具有抗性. 这一发现揭示了新的病毒RNA机制,可能会影响疾病.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 在RNA分离过程中.
背景情况:
- 疹病毒操纵宿主基因表达以进行病毒复制.
- 替代拼接,包括循环RNA (circRNA) 合成,是基因调节的一个关键领域.
- 了解病毒circRNA对于破译病毒生命周期至关重要.
研究的目的:
- 为了研究循环RNA (circRNA) 合成中的α-和gamma-herpesvirus诱导的改变.
- 在临床和潜伏感染期间识别和描述病毒circRNAs.
- 探索调节病毒circRNA产生的机制.
主要方法:
- 开发"宿主和病毒中的Circrnas anaLysis pIpEline" (CHARLIE) 用于病毒circRNA分析.
- 通过测序来识别反向拼接变体.
- 对宿主RNA连接酶 (RTCB,RLIG1) 的功能丧失研究.
- 通过eCLIP和4sU测序来评估KSHVORF57.5的作用.
主要成果:
- 数以千计的病毒性circRNAs被确定,这些circRNAs在临床和潜伏性疹病毒感染中都很常见.
- 首次报告疹简单病毒-1 circRNAs,包括来自ICP0和延迟相关转录的.
- 病毒circRNAs表现出对结合体抑制的抗性,并且缺乏正规的结合位.
- 宿主RNA连接酶影响了病毒的背部拼接,KSHV ORF57增强了病毒和宿主circRNA的合成.
结论:
- 疹病毒在炎症感染期间使用独特的拼接机制来产生circRNAs.
- 病毒circRNAs代表了一种新型的转录类,在疹病毒复制,持久性和瘤发生方面具有潜在的作用.
- 这项研究为进一步研究病毒circRNAs的功能意义提供了基础.
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