Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Nucleic Acids Res. 2019 Nov 4;47(19):10027-10039. doi: 10.1093/nar/gkz781.
Alternative polyadenylation (APA) is emerging as an important layer of gene regulation because the majority of mammalian protein-coding genes contain multiple polyadenylation (pA) sites in their 3' UTR. By alteration of 3' UTR length, APA can considerably affect post-transcriptional gene regulation. Yet, our understanding of APA remains rudimentary. Novel single-cell RNA sequencing (scRNA-seq) techniques allow molecular characterization of different cell types to an unprecedented degree. Notably, the most popular scRNA-seq protocols specifically sequence the 3' end of transcripts. Building on this property, we implemented a method for analysing patterns of APA regulation from such data. Analyzing multiple datasets from diverse tissues, we identified widespread modulation of APA in different cell types resulting in global 3' UTR shortening/lengthening and enhanced cleavage at intronic pA sites. Our results provide a proof-of-concept demonstration that the huge volume of scRNA-seq data that accumulates in the public domain offers a unique resource for the exploration of APA based on a very broad collection of cell types and biological conditions.
可变多聚腺苷酸化(APA)正成为基因调控的一个重要层面,因为大多数哺乳动物的蛋白编码基因在其 3'UTR 中含有多个多聚腺苷酸化(pA)位点。通过改变 3'UTR 长度,APA 可以显著影响转录后基因调控。然而,我们对 APA 的理解仍然很初步。新型的单细胞 RNA 测序(scRNA-seq)技术允许对不同细胞类型进行前所未有的分子特征分析。值得注意的是,最流行的 scRNA-seq 方案专门对转录本的 3'端进行测序。基于这一特性,我们开发了一种从这些数据中分析 APA 调控模式的方法。通过分析来自不同组织的多个数据集,我们在不同的细胞类型中发现了 APA 的广泛调节,导致全局 3'UTR 缩短/延长和增强内含子 pA 位点的切割。我们的结果提供了一个概念验证,即公共领域中积累的大量 scRNA-seq 数据为基于非常广泛的细胞类型和生物条件探索 APA 提供了独特的资源。