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首页> 外文期刊>Nucleic Acids Research >Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs
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Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs

机译：人类生存电机神经元基因产生巨大的圆形rnas

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摘要

Circular RNAs (circRNAs) perform diverse functions, including the regulation of transcription, translation, peptide synthesis, macromolecular sequestration and trafficking. Inverted Alu repeats capable of forming RNA:RNA duplexes that bring splice sites together for backsplicing are known to facilitate circRNA generation. However, higher limits of circRNAs produced by a single Alu-rich gene are currently not predictable due to limitations of amplification and analyses. Here, using a tailored approach, we report a surprising diversity of exon-containing circRNAs generated by the Alu-rich Survival Motor Neuron (SMN) genes that code for SMN, an essential multifunctional protein in humans. We show that expression of the vast repertoire of SMN circRNAs is universal. Several of the identified circRNAs harbor novel exons derived from both intronic and intergenic sequences. A comparison with mouse Smn circRNAs underscored a clear impact of primate-specific Alu elements on shaping the overall repertoire of human SMN circRNAs. We show the role of DHX9, an RNA helicase, in splicing regulation of several SMN exons that are preferentially incorporated into circRNAs. Our results suggest self- and cross-regulation of biogenesis of various SMN circRNAs. These findings bring a novel perspective towards a better understanding of SMN gene function.
机译：环状RNA（circRNAs）执行各种功能，包括转录，翻译，肽合成，高分子多价螯合和贩卖的调节。倒置的Alu重复能够形成RNA的：双链RNA带来剪接位点一起backsplicing已知促进circRNA产生。然而，由单个ALU-富基因产生circRNAs的高限，目前不扩增和分析的局限性可预测的到期。在这里，用量身定制的方法，我们报告由ALU富含运动神经元生存（SMN）基因产生的含外显子circRNAs的一个惊人的多样性，对于SMN，在人体必需的多功能蛋白代码。我们展示SMN circRNAs广大剧目的表达是普遍的。其中一些已确定的circRNAs窝藏来自内含子和基因间序列的新颖的外显子。与小鼠的Smn circRNAs比较强调塑造人类SMN circRNAs的整体剧目特定灵长类动物的Alu元件的明显的影响。我们发现DHX9，一个RNA解旋酶的作用，在被优先纳入circRNAs几个SMN外显子剪接调节。我们的研究结果表明不同SMN circRNAs的生物合成的自我和交叉调节。这些发现使朝着更好地了解SMN基因功能的一种新的视角。

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