ArticleGenome research2013
A broadly applicable high-throughput screening strategy identifies new regulators of Dlg4 (Psd-95) alternative splicing.
Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- SPLiCR-seq: A CRISPR-Based Screening Platform for RNA splicing Identifies Novel Regulators of IRE1α-XBP1 Signaling Under ER Stress.Nature communications · 2025Article
- Expression pattern, immune signature, and prognostic value of RBM10 in human cancers.Histology and histopathology · 2025Article
- Splicing to orchestrate cell fate.Molecular therapy. Nucleic acids · 2025Review
- Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.Nature biotechnology · 2024Article
- The Art of Finding the Right Drug Target: Emerging Methods and Strategies.Pharmacological reviews · 2024Review
- CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements.Nature communications · 2024Article
- Article
- Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing.Nature communications · 2024Article
- Article
- A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses.Neuron · 2023Article
- Cell-specific regulation of gene expression using splicing-dependent frameshifting.Nature communications · 2022Article
- Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance.International journal of molecular sciences · 2021Article
- Review
- Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of theInternational journal of molecular sciences · 2020Article
- RBM10, a New Regulator of p53.Cells · 2020Review
- The Secret Garden of Neuronal circRNAs.Cells · 2020Review
- In vivo Reporters for Visualizing Alternative Splicing of Hormonal Genes.Plants (Basel, Switzerland) · 2020Article
- Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Review
- A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.Nucleic acids research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Most mammalian genes produce multiple mRNA isoforms derived from alternative pre-mRNA splicing, with each alternative exon controlled by a complex network of regulatory factors. The identification of these regulators can be laborious and is usually carried out one factor at a time. We have developed a broadly applicable high-throughput screening method that simultaneously identifies multiple positive and negative regulators of a particular exon. Two minigene reporters were constructed: One produces green fluorescent protein (GFP) from the mRNA including an exon, and red fluorescent protein (RFP) from the mRNA lacking the exon; the other switches these fluorescent products of exon inclusion and exclusion. Combining results from these two reporters eliminates many false positives and greatly enriches for true splicing regulators. After extensive optimization of this method, we performed a gain-of-function screen of 15,779 cDNA clones and identified 40 genes affecting exon 18 of Discs large homolog 4 (Dlg4; also known as post-synaptic density protein 95 [Psd-95]). We confirmed that 28 of the 34 recoverable clones alter reporter splicing in RT-PCR assays. Remarkably, 18 of the identified genes encode splicing factors or RNA binding proteins, including PTBP1, a previously identified regulator of this exon. Loss-of-function experiments examining endogenous Dlg4 transcripts validated the effects of five of eight genes tested in independent cell lines, and two genes were further confirmed to regulate Dlg4 splicing in primary neurons. These results identify multiple new regulators of Dlg4 splicing, and validate an approach to isolating splicing regulators for almost any cassette exon from libraries of cDNAs, shRNAs, or small molecules.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.