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。
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
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.