ArticlePLoS biology2005
A combinatorial code for splicing silencing: UAGG and GGGG motifs.
Article in PLoS biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
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- The striatal heterogeneous nuclear ribonucleoprotein H1 mRNA targetome associated with methamphetamine administration and behavior.Progress in neuro-psychopharmacology & biological psychiatry · 2026Article
- The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.Genes & development · 2025Article
- hnRNP H controls alternative splicing of human papillomavirus type 16 E1, E6, E7, and E6^E7 mRNAs via GGG motifs.Journal of virology · 2024Article
- A single-cell strategy for the identification of intronic variants related to mis-splicing in pancreatic cancer.NAR genomics and bioinformatics · 2024Article
- An intronic RNA element modulates Factor VIII exon-16 splicing.Nucleic acids research · 2024Article
- Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.iScience · 2023Article
- Suppression of hnRNP A1 binding to HK1 RNA leads to glycolytic dysfunction in Alzheimer's disease models.Frontiers in aging neuroscience · 2023Article
- Knockdown of hnRNPA1 Promotes NSCLC Metastasis and EMT by Regulating Alternative Splicing of LAS1L exon 9.Frontiers in oncology · 2022Article
- hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.Frontiers in pharmacology · 2022Review
- miRNA-Based Regulation of Alternative RNA Splicing in Metazoans.International journal of molecular sciences · 2021Review
- Multiple Sclerosis-Associated hnRNPA1 Mutations Alter hnRNPA1 Dynamics and Influence Stress Granule Formation.International journal of molecular sciences · 2021Article
- A Comprehensive Analysis of the Role of hnRNP A1 Function and Dysfunction in the Pathogenesis of Neurodegenerative Disease.Frontiers in molecular biosciences · 2021Review
- HNRNPH1-dependent splicing of a fusion oncogene reveals a targetable RNA G-quadruplex interaction.RNA (New York, N.Y.) · 2019Article
- Thioflavin T Monitoring of Guanine Quadruplex Formation in the rs689-Dependent INS Intron 1.Molecular therapy. Nucleic acids · 2019Article
- MMSplice: modular modeling improves the predictions of genetic variant effects on splicing.Genome biology · 2019Article
- Exploring the suitability of RanBP2-type Zinc Fingers for RNA-binding protein design.Scientific reports · 2019Article
- TCF3 alternative splicing controlled by hnRNP H/F regulates E-cadherin expression and hESC pluripotency.Genes & development · 2018Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes.
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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.