Comprehensive Mapping of Alternative Polyadenylation Site Usage and Its Dynamics at Single-cell Resolution

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Dec 1

PMID 36454750

Authors

Junliang Wang

Wei Chen

Wenjun Yue

Wenhong Hou

Feng Rao

Hanbing Zhong

Yuanming Qi

Ni Hong

Ting Ni

Wenfei Jin

Affiliations

Soon will be listed here.

Abstract

Alternative polyadenylation (APA) plays an important role in posttranscriptional gene regulation such as transcript stability and translation efficiency. However, our knowledge about APA dynamics at the single-cell level is largely unexplored. Here, we developed single-cell polyadenylation sequencing, a strand-specific approach for sequencing the 3' end of transcripts, to investigate the landscape of APA at the single-cell level. By analyzing several cell lines, we found many genes using multiple polyA sites in bulk data are prone to use only one polyA site in each single cell. Interestingly, cell cycle genes were significantly enriched in genes with high variation in polyA site usages. Furthermore, the 414 genes showing a polyA site usage switch after cell synchronization enriched cell cycle genes, while the differentially expressed genes after cell synchronization did not enrich cell cycle genes. We further identified 812 genes showing polyA site usage changes between neighboring cell cycles, which were grouped into six clusters, with cell phase-specific functional categories enriched in each cluster. Deletion of one polyA site in and results in slower and faster cell cycle progression, respectively, supporting polyA site usage switch played an important role in cell cycle. These results indicate that APA is an important layer for cell cycle regulation.

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