CPA-Perturb-seq: Multiplexed single-cell characterization of alternative polyadenylation regulators.

ABSTRACT: Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity that is governed by the cleavage and polyadenylation (CPA) regulatory machinery. To better understand how these proteins govern polyA site choice we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 known CPA regulators with a 3' scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a statistical framework to specifically identify perturbation-dependent changes in intronic and tandem polyadenylation, and discover modules of co-regulated polyA sites exhibiting distinct functional properties. By training a multi-task deep neural network (APARENT-Perturb) on our dataset, we delineate a cis-regulatory code that predicts

SUBMITTER: Kowalski MH 

PROVIDER: S-EPMC9934614 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature