Cell-type-specific analysis of alternative polyadenylation using single-cell transcriptomics data

Abstract

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.