Filippenkov Ivan B, Kalinichenko Eugene O, Limborska Svetlana A, Dergunova Lyudmila V
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
Neurogenetics. 2017 Jan;18(1):1-6. doi: 10.1007/s10048-016-0490-4. Epub 2016 Jul 23.
Circular RNAs (circRNAs) provide a new and relatively unexplored class of noncoding RNAs that are predominantly found in mammalian cells. In this review, we present the latest data regarding the structural organization, possible mechanisms of synthesis, and functions of circRNAs. These transcripts were isolated as an RNA fraction that was resistant to RNase R treatment, which selectively destroys the linear forms of RNA molecules. circRNAs are encoded by orthologous genes in different organisms and show tissue- and organ-specific expression. Currently, the biogenesis and functional properties of circRNAs remain unclear; transcripts of this class, however, remain highly promising targets of research. Some of them have been ascribed the function of "molecular sponges" that can absorb microRNAs, RNA-binding proteins, and small nuclear RNAs. circRNAs are often formed from the RNA portions of protein-coding genes in the course of alternative splicing. Some features of the circRNAs of mammals were demonstrated using 11 circRNAs of the human sphingomyelin synthase 1 gene (SGMS1), which were discovered by us in the brain. These circRNAs consist mainly of portions of the multi-exon 5' untranslated region (5'UTR) of the SGMS1 gene and include one to five exons. The synthesis of circRNAs may be new, previously unknown, function of the multi-exon 5'UTR of genes. This feature is most clearly manifested in the brain, where the level of circRNAs is significantly higher.
环状RNA(circRNAs)是一类新的、相对未被充分探索的非编码RNA,主要存在于哺乳动物细胞中。在本综述中,我们展示了关于circRNAs的结构组织、可能的合成机制和功能的最新数据。这些转录本作为对RNase R处理具有抗性的RNA组分被分离出来,RNase R可选择性地破坏RNA分子的线性形式。circRNAs由不同生物体中的直系同源基因编码,并表现出组织和器官特异性表达。目前,circRNAs的生物发生和功能特性仍不清楚;然而,这类转录本仍然是非常有前景的研究靶点。其中一些被赋予了“分子海绵”的功能,能够吸收微小RNA、RNA结合蛋白和小核RNA。circRNAs通常在可变剪接过程中由蛋白质编码基因的RNA部分形成。我们在大脑中发现的人类鞘磷脂合酶1基因(SGMS1)的11种circRNAs展示了哺乳动物circRNAs的一些特征。这些circRNAs主要由SGMS1基因的多外显子5'非翻译区(5'UTR)的部分组成,包含一到五个外显子。circRNAs的合成可能是基因多外显子5'UTR的一种新的、以前未知的功能。这一特征在大脑中表现得最为明显,其中circRNAs的水平显著更高。