Department of Anesthesia, The First Affiliated Hospital, School of medicine, Zhejiang University, Zhejiang, China.
Mol Cells. 2013 Dec;36(6):518-26. doi: 10.1007/s10059-013-0171-1. Epub 2013 Nov 14.
MicroRNAs are short 21-22 nucleotide single strand RNAs that are involved in post-transcriptional regulation of gene expression. Most microRNAs are first transcribed as long primary microRNAs and then undergo a two step-wise sequential processing to yield single-stranded mature microRNAs. It has been suggested that the loop region of primary microRNAs plays an important role in regulating microRNA biogenesis and target recognition. However, despite the fact that several single nucleotide polymorphisms have been identified in mature microRNA sequences and are related to human diseases, it remains unclear whether and how the single nucleotide polymorphisms in the loop regions of primary microRNAs would affect the biogenesis and function of microRNAs. Herein, we provide evidence that primary microRNAs loop nucleotides control the accuracy and efficiency of microRNA processing. Accordingly, we identified 32 single nucleotide polymorphisms in the loop regions of human primary microRNAs using bioinformatics, and further validated three loss-of-function and one gain-of-function single nucleotide polymorphisms using dual-luciferase assays. Thus, these results reveal a critical regulatory role encoded in the loop nucleotides of primary microRNAs for microRNA processing and function.
微 RNA 是参与基因表达转录后调控的短 21-22 个核苷酸单链 RNA。大多数微 RNA 最初作为长的初级微 RNA 转录，然后经过两步连续加工产生单链成熟的微 RNA。有人认为初级微 RNA 的环区在调节微 RNA 生物发生和靶标识别中起重要作用。然而，尽管已经在成熟微 RNA 序列中鉴定出几个与人类疾病相关的单核苷酸多态性，但尚不清楚初级微 RNA 环区的单核苷酸多态性是否以及如何影响微 RNA 的生物发生和功能。本文中，我们提供了初级微 RNA 环核苷酸控制微 RNA 加工准确性和效率的证据。因此，我们使用生物信息学在人类初级微 RNA 的环区中鉴定出 32 个单核苷酸多态性，并进一步使用双荧光素酶报告基因实验验证了三个失活功能和一个获得功能的单核苷酸多态性。因此，这些结果揭示了初级微 RNA 环核苷酸对微 RNA 加工和功能的关键调节作用。
