新加坡基因组研究所Yue Wan、Jiaxu Wang研究组取得新进展。他们利用单细胞水平RNA结构剖析揭示了新的细胞特征决定因素。相关论文于2024年1月4日发表在《自然—方法学》杂志上。

研究人员受SHAPE的启发开发了一种单细胞RNA转录本结构探测方法，它能以单细胞分辨率同时测定转录本的二级结构和丰度。研究将单细胞RNA转录本结构探测应用于人胚胎干细胞和分化的神经元。值得注意的是，与神经元相比，人胚胎干细胞中的RNA结构更加均匀，编码区的均匀度最高。3′非翻译区的异质性更广泛，由特定的RNA结合蛋白决定。

整体RNA结构图比单独的基因表达图谱更能区分细胞类型特征和分化阶段。研究人员进一步发现了18S核糖体RNA的细胞类型可变区，它与细胞周期和翻译控制有关。该方法为系统描述单细胞水平RNA的结构-功能关系打开了大门。

据介绍，RNA结构对基因调控的多个步骤至关重要。然而，尚不清楚转录本的结构在单个细胞内和细胞间有何差异。

附：英文原文

Title: RNA structure profiling at single-cell resolution reveals new determinants of cell identity

Author: Wang, Jiaxu, Zhang, Yu, Zhang, Tong, Tan, Wen Ting, Lambert, Finnlay, Darmawan, Jefferson, Huber, Roland, Wan, Yue

Issue&Volume: 2024-01-04

Abstract: RNA structure is critical for multiple steps in gene regulation. However, how the structures of transcripts differ both within and between individual cells is unknown. Here we develop a SHAPE-inspired method called single-cell structure probing of RNA transcripts that enables simultaneous determination of transcript secondary structure and abundance at single-cell resolution. We apply single-cell structure probing of RNA transcripts to human embryonic stem cells and differentiating neurons. Remarkably, RNA structure is more homogeneous in human embryonic stem cells compared with neurons, with the greatest homogeneity found in coding regions. More extensive heterogeneity is found within 3′ untranslated regions and is determined by specific RNA-binding proteins. Overall RNA structure profiles better discriminate cell type identity and differentiation stage than gene expression profiles alone. We further discover a cell-type variable region of 18S ribosomal RNA that is associated with cell cycle and translation control. Our method opens the door to the systematic characterization of RNA structure–function relationships at single-cell resolution.

DOI: 10.1038/s41592-023-02128-y

Source: https://www.nature.com/articles/s41592-023-02128-y