Misir Sema, Wu Nan, Yang Burton B
Sunnybrook Research Institute, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Cell Death Differ. 2022 Mar;29(3):481-491. doi: 10.1038/s41418-022-00948-7. Epub 2022 Feb 15.
In recent years, circular RNAs (circRNAs), a new class of RNA molecules characterized by their covalently closed circular structure, have become a new research paradigm in RNA biology. Many circRNAs are conserved among eukaryotes, localize in specific subcellular compartments, and play different biological roles. Accumulating evidence shows that circRNAs regulate a diversity of cellular processes by acting as miRNA sponges, anchors for circRNA binding proteins (cRBPs), transcriptional regulators, molecular scaffolds, and sources for translation of small proteins/peptides. The emergence of the biological functions of circRNAs has brought a new perspective to our understanding of cellular physiology and disease pathogenesis. Recent studies have shown that the expression of circRNAs is tissue- and cell type-specific and specifically regulated through development or disease progression, where they exert specific biological functions. However, the mechanisms underlying these remain largely unknown. A deeper understanding of how the specific expression of circRNAs is regulated to exert specific biological functions will enable the use of circRNA as a biomarker in clinical practice and the development of new therapeutic approaches. This review aims to summarize recent developments in circRNA biogenesis, functions, and molecular mechanisms. We also provide some specific circRNAs as examples to show their tissue-specific distribution and evaluate the possibility of applying circRNA technologies in molecular research and therapeutics.
近年来，环状RNA（circRNAs）作为一类以共价闭合环状结构为特征的新型RNA分子，已成为RNA生物学领域的一种新研究范式。许多circRNAs在真核生物中保守存在，定位于特定的亚细胞区室，并发挥不同的生物学作用。越来越多的证据表明，circRNAs通过充当微小RNA（miRNA）海绵、circRNA结合蛋白（cRBPs）的锚定物、转录调节因子、分子支架以及小蛋白/肽翻译的来源，来调节多种细胞过程。circRNAs生物学功能的出现为我们理解细胞生理学和疾病发病机制带来了新的视角。最近的研究表明，circRNAs的表达具有组织和细胞类型特异性，并在发育或疾病进展过程中受到特异性调控，在其中发挥特定的生物学功能。然而，其潜在机制在很大程度上仍不清楚。深入了解circRNAs的特异性表达是如何被调控以发挥特定生物学功能，将有助于在临床实践中把circRNA用作生物标志物，并开发新的治疗方法。本综述旨在总结circRNA生物合成、功能及分子机制方面的最新进展。我们还提供了一些特定的circRNAs作为实例，以展示它们的组织特异性分布，并评估在分子研究和治疗中应用circRNA技术的可能性。
