Sadeq Shaymaa, Al-Hashimi Surar, Cusack Carmen M, Werner Andreas
Biosciences Institute, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Noncoding RNA. 2021 Feb 19;7(1):15. doi: 10.3390/ncrna7010015.
The birth of long non-coding RNAs (lncRNAs) is closely associated with the presence and activation of repetitive elements in the genome. The transcription of endogenous retroviruses as well as long and short interspersed elements is not only essential for evolving lncRNAs but is also a significant source of double-stranded RNA (dsRNA). From an lncRNA-centric point of view, the latter is a minor source of bother in the context of the entire cell; however, dsRNA is an essential threat. A viral infection is associated with cytoplasmic dsRNA, and endogenous RNA hybrids only differ from viral dsRNA by the 5' cap structure. Hence, a multi-layered defense network is in place to protect cells from viral infections but tolerates endogenous dsRNA structures. A first line of defense is established with compartmentalization; whereas endogenous dsRNA is found predominantly confined to the nucleus and the mitochondria, exogenous dsRNA reaches the cytoplasm. Here, various sensor proteins recognize features of dsRNA including the 5' phosphate group of viral RNAs or hybrids with a particular length but not specific nucleotide sequences. The sensors trigger cellular stress pathways and innate immunity via interferon signaling but also induce apoptosis via caspase activation. Because of its central role in viral recognition and immune activation, dsRNA sensing is implicated in autoimmune diseases and used to treat cancer.
长链非编码RNA（lncRNA）的产生与基因组中重复元件的存在和激活密切相关。内源性逆转录病毒以及长短散在元件的转录不仅是lncRNA进化所必需的，也是双链RNA（dsRNA）的重要来源。从以lncRNA为中心的角度来看，在整个细胞环境中，后者是一个较小的麻烦来源；然而，dsRNA却是一个重大威胁。病毒感染与细胞质中的dsRNA相关，内源性RNA杂交体与病毒dsRNA的区别仅在于5'帽结构。因此，存在一个多层防御网络来保护细胞免受病毒感染，但能耐受内源性dsRNA结构。第一道防线是通过区室化建立的；内源性dsRNA主要局限于细胞核和线粒体，而外源性dsRNA会进入细胞质。在这里，各种传感蛋白识别dsRNA的特征，包括病毒RNA或特定长度杂交体的5'磷酸基团，但不识别特定的核苷酸序列。这些传感器通过干扰素信号触发细胞应激途径和先天免疫，也通过半胱天冬酶激活诱导细胞凋亡。由于其在病毒识别和免疫激活中的核心作用，dsRNA传感与自身免疫性疾病有关，并被用于治疗癌症。
