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纳米孔长读技术可确定同工型特异性RNA结构
作者:小柯机器人 发布时间:2020/10/28 15:07:02

新加坡基因组研究所Yue Wan、Niranjan Nagarajan等研究人员合作发现,纳米孔长读技术可确定同工型特异性RNA结构。2020年10月26日,《自然—生物技术》杂志在线发表了这项成果。

研究人员报道了使用纳米孔测序(PORE-cupine)进行RNA结构分析的方法,其可将使用化学修饰的结构探测与直接的长读RNA测序与机器学习相结合,从而检测细胞RNA中的二级结构。PORE-cupine还捕获了整体结构特征,例如RNA结合蛋白结合位点和单核苷酸变体的反应性差异。
 
研究人员发现,相同基因不同转录亚型中的共享序列可以折叠成不同的结构,这突显出了长读测序对获得阶段性信息的重要性。研究人员还证明了同一基因转录同工型之间的结构差异会导致翻译效率的不同。通过揭示同工型特异的RNA结构,PORE-cupine将加深对结构在控制基因调控中作用的了解。
 
据了解,目前使用短读测序法来确定RNA结构的方法无法捕获不同转录本同工型之间的大量差异。
 
附:英文原文

Title: Determination of isoform-specific RNA structure with nanopore long reads

Author: Jong Ghut Ashley Aw, Shaun W. Lim, Jia Xu Wang, Finnlay R. P. Lambert, Wen Ting Tan, Yang Shen, Yu Zhang, Pornchai Kaewsapsak, Chenhao Li, Sarah B. Ng, Leah A. Vardy, Meng How Tan, Niranjan Nagarajan, Yue Wan

Issue&Volume: 2020-10-26

Abstract: Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. We show that shared sequences in different transcript isoforms of the same gene can fold into different structures, highlighting the importance of long-read sequencing for obtaining phase information. We also demonstrate that structural differences between transcript isoforms of the same gene lead to differences in translation efficiency. By revealing isoform-specific RNA structure, PORE-cupine will deepen understanding of the role of structures in controlling gene regulation. 

DOI: 10.1038/s41587-020-0712-z

Source: https://www.nature.com/articles/s41587-020-0712-z

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex