Using Drosophila to uncover molecular and physiological functions of circRNAs.
Using Drosophila to uncover molecular and physiological functions of circRNAs.
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DOI：
10.1016/j.ymeth.2021.04.016
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Kadener S
中科院分区：
文献类型：
--
作者：
Krishnamoorthy A;Kadener S
环状RNA（circRNA）是一类通过反向剪接产生的共价闭合的RNA分子。circRNA以组织特异性方式表达，随着年龄的增长在神经组织中积累，并且高度稳定。在许多情况下，circRNA是以线性转录物为代价产生的，因为反向剪接与线性剪接竞争。一些circRNA以顺式调节基因表达，并且一些circRNA可以翻译成蛋白质。深度测序和新的生物信息学工具的出现允许在真核生物中检测数千个circRNA。研究circRNA的功能是使用分子和遗传方法的组合进行的。可用于果蝇研究的独特遗传工具是破译体内circRNA功能的理想工具。这些工具包括GAL 4-UAS系统，该系统可用于通过精确的时间和空间控制来操纵circRNA的水平，以及遗传相互作用筛选，该筛选可用于识别由circRNA调节的途径。在果蝇中进行的研究揭示了circRNA的产生机制，它们的翻译细节及其生理功能。由于它们的生命周期短，并且存在优秀的神经退行性疾病模型，果蝇也可以用于研究circRNA在衰老和年龄相关疾病中的作用。在这里，我们审查分子和遗传工具和方法检测，操纵和研究果蝇circRNA。
Circular RNAs (circRNAs) are a class of covalently closed RNA molecules generated by backsplicing. circRNAs are expressed in a tissue-specific manner, accumulate with age in neural tissues, and are highly stable. In many cases, circRNAs are generated at the expense of a linear transcript as back-splicing competes with linear splicing. Some circRNAs regulate gene expression in cis, and some circRNAs can be translated into protein. The advent of deep sequencing and new bioinformatic tools has allowed detection of thousands of circRNAs in eukaryotes. Studying the functions of circRNAs is done using a combination of molecular and genetic methods. The unique genetic tools that can be used in studies of Drosophila melanogaster are ideal for deciphering the functions of circRNAs in vivo. These tools include the GAL4-UAS system, which can be used to manipulate the levels of circRNAs with exquisite temporal and spatial control, and genetic interaction screening, which could be used to identify pathways regulated by circRNAs. Research performed in Drosophila has revealed circRNAs production mechanisms, details of their translation, and their physiological functions. Due to their short lifecycle and the existence of excellent neurodegeneration models, Drosophila can also be used to study the role of circRNAs in aging and age-related disorders. Here, we review molecular and genetic tools and methods for detecting, manipulating, and studying circRNAs in Drosophila.
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