环形RNA在天然免疫过程中的重要功能

Circular RNAs in innate immunity

一类环形RNA来自外显子反向剪接,以共价键形成闭环结构。至今,科学家在真核生物中发现了多达几十万条环形RNA,但大部分环形RNA的功能至今不详。中国科学院生物化学与细胞生物学研究所陈玲玲研究组与合作者的最新研究成果阐述了环形RNA在细胞受病毒感染时的降解机制及其通过形成分子内双链结构结合天然免疫因子参与天然免疫应答调控的重要新功能,并揭示环形RNA低表达与炎症性自身免疫性病——系统性红斑狼疮(systemic lupus erythematosus, SLE)密切相关。该研究为环形RNA在天然免疫中的重要功能研究奠定基础,并为炎症性自身免疫病的发病机制及未来的干预治疗提出了新的思路与潜在靶点。

A large number of circular RNAs(circRNAs)produced from precursor mRNA(pre-mRNA)back-splicing of exon(s)have been identified in metazoans.Functions of most circRNAs remain largely unexplored.In a recent study published at Cell,Research team led by Dr.Ling-Ling Chen at Shanghai Institute of Biochemistry and Cell Biology of Chinese Academy of Sciences and her collaborators uncovered upon poly(I:C)stimulation or viral infection,circRNAs are globally degraded by RNase L,a process required for PKR activation in early cellular innate immune responses.They also identified that many examined circRNAs tend to form 16-26 bp long intra-molecularly imperfect RNA duplexes,and circRNAs preferentially bind to dsRNA-activated protein kinase(PKR)related to innate immunity and act as PKR inhibitors.Dysregulation of circRNAs expression and PKR activation is linked to the autoimmune disease systemic lupus erythematosus(SLE).This study uncovered circRNAs function in innate immunity and also an unexpected pathophysiological connection of circRNAs to autoimmune diseases.