ArticlePLoS genetics2020
A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex.PLoS pathogens · 2026Article
- Systematic identification and characterization of regulators of aryl hydrocarbon receptor signaling.bioRxiv : the preprint server for biology · 2025Article
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- Engineering novel CRISPRi repressors for highly efficient mammalian gene regulation.Genome biology · 2025Article
- dFLASH; dual FLuorescent transcription factor activity sensor for histone integrated live-cell reporting and high-content screening.Nature communications · 2025Article
- An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation.Nature chemical biology · 2025Article
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-wide pan-GPCR cell libraries accelerate drug discovery.Acta pharmaceutica Sinica. B · 2024Review
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.bioRxiv : the preprint server for biology · 2024Article
- Quantitative proteomics reveals CLR interactome in primary human cells.The Journal of biological chemistry · 2024Article
- Endosome positioning coordinates spatially selective GPCR signaling.Nature chemical biology · 2024Article
- CRISPR applications in cancer diagnosis and treatment.Cellular & molecular biology letters · 2023Review
- The psychosis risk factorbioRxiv : the preprint server for biology · 2023Article
- Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors.eLife · 2022Article
- DNA primase subunit 1 deteriorated progression of hepatocellular carcinoma by activating AKT/mTOR signaling and UBE2C-mediated P53 ubiquitination.Cell & bioscience · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) allow cells to respond to chemical and sensory stimuli through generation of second messengers, such as cyclic AMP (cAMP), which in turn mediate a myriad of processes, including cell survival, proliferation, and differentiation. In order to gain deeper insights into the complex biology and physiology of these key cellular pathways, it is critical to be able to globally map the molecular factors that shape cascade function. Yet, to this date, efforts to systematically identify regulators of GPCR/cAMP signaling have been lacking. Here, we combined genome-wide screening based on CRISPR interference with a novel sortable transcriptional reporter that provides robust readout for cAMP signaling, and carried out a functional screen for regulators of the pathway. Due to the sortable nature of the platform, we were able to assay regulators with strong and moderate phenotypes by analyzing sgRNA distribution among three fractions with distinct reporter expression. We identified 45 regulators with strong and 50 regulators with moderate phenotypes not previously known to be involved in cAMP signaling. In follow-up experiments, we validated the functional effects of seven newly discovered mediators (NUP93, PRIM1, RUVBL1, PKMYT1, TP53, SF3A2, and HRAS), and showed that they control distinct steps of the pathway. Thus, our study provides proof of principle that the screening platform can be applied successfully to identify bona fide regulators of GPCR/second messenger cascades in an unbiased and high-throughput manner, and illuminates the remarkable functional diversity among GPCR regulators.
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