Dissecting key regulators of transcriptome kinetics through scalable single-cell RNA profiling of pooled CRISPR screens.

Xu, Zihan; Sziraki, Andras; Lee, Jasper; Zhou, Wei; Cao, Junyue · Nat Biotechnol · 2024

basic_science · Level V

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Abstract

We present a combinatorial indexing method, PerturbSci-Kinetics, for capturing whole transcriptomes, nascent transcriptomes and single guide RNA (sgRNA) identities across hundreds of genetic perturbations at the single-cell level. Profiling a pooled CRISPR screen targeting various biological processes, we show the gene expression regulation during RNA synthesis, processing and degradation, miRNA biogenesis and mitochondrial mRNA processing, systematically decoding the genome-wide regulatory network that underlies RNA temporal dynamics at scale.

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