ArticleProceedings of the National Academy of Sciences of the United States of America2003
Inhibiting expression of specific genes in mammalian cells with 5' end-mutated U1 small nuclear RNAs targeted to terminal exons of pre-mRNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 78 citations in OpenAlex.
- Utargetome: A targetome prediction tool for modified U1-snRNAs to identify distal-target positions with improved selectivity.PLoS computational biology · 2025Article
- A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance.Molecular cell · 2025Article
- Article
- Regulation of alternative splicing and polyadenylation in neurons.Life science alliance · 2023Review
- U1A is a positive regulator of the expression of heterologous and cellular genes involved in cell proliferation and migration.Molecular therapy. Nucleic acids · 2022Article
- ZFC3H1 and U1-70K promote the nuclear retention of mRNAs with 5' splice site motifs within nuclear speckles.RNA (New York, N.Y.) · 2022Article
- A Reporter Based Cellular Assay for Monitoring Splicing Efficiency.Journal of visualized experiments : JoVE · 2021Article
- Emerging Roles of RNA 3'-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders.Biomolecules · 2020Review
- High-throughput identification of synthetic riboswitches by barcode-free amplicon-sequencing in human cells.Nature communications · 2020Article
- U1 snRNP Telescripting: Suppression of Premature Transcription Termination in Introns as a New Layer of Gene Regulation.Cold Spring Harbor perspectives in biology · 2019Review
- Nucleotide Modifications Decrease Innate Immune Response Induced by Synthetic Analogs of snRNAs and snoRNAs.Genes · 2018Article
- Sequence Determinants for Nuclear Retention and Cytoplasmic Export of mRNAs and lncRNAs.Frontiers in genetics · 2018Review
- Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA.PLoS genetics · 2017Article
- The reciprocal regulation between splicing and 3'-end processing.Wiley interdisciplinary reviews. RNA · 2016Review
- Conditional U1 Gene Silencing in Toxoplasma gondii.PloS one · 2015Article
- Morphine regulates expression of μ-opioid receptor MOR-1A, an intron-retention carboxyl terminal splice variant of the μ-opioid receptor (OPRM1) gene via miR-103/miR-107.Molecular pharmacology · 2014Article
- Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors.Frontiers in endocrinology · 2014Article
- U1 adaptors for the therapeutic knockdown of the oncogene pim-1 kinase in glioblastoma.Nucleic acid therapeutics · 2013Article
- Splicing-coupled 3' end formation requires a terminal splice acceptor site, but not intron excision.Nucleic acids research · 2013Article
- A simple model to explain evolutionary trends of eukaryotic gene architecture and expression: how competition between splicing and cleavage/polyadenylation factors may affect gene expression and splice-site recognition in eukaryotes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Reducing or eliminating expression of a given gene is likely to require multiple methods to ensure coverage of all of the genes in a given mammalian cell. We and others [Furth, P. A., Choe, W. T., Rex, J. H., Byrne, J. C., and Baker, C. C. (1994) Mol. Cell. Biol. 14, 5278-5289] have previously shown that U1 small nuclear (sn) RNA, both natural or with 5' end mutations, can specifically inhibit reporter gene expression in mammalian cells. This inhibition occurs when the U1 snRNA 5' end base pairs near the polyadenylation signal of the reporter gene's pre-mRNA. This base pairing inhibits poly(A) tail addition, a key, nearly universal step in mRNA biosynthesis, resulting in degradation of the mRNA. Here we demonstrate that expression of endogenous mammalian genes can be efficiently inhibited by transiently or stably expressed 5' end-mutated U1 snRNA. Also, we determine the inhibitory mechanism and establish a set of rules to use this technique and to improve the efficiency of inhibition. Two U1 snRNAs base paired to a single pre-mRNA act synergistically, resulting in up to 700-fold inhibition of the expression of specific reporter genes and 25-fold inhibition of endogenous genes. Surprisingly, distance from the U1 snRNA binding site to the poly(A) signal is not critical for inhibition, instead the U1 snRNA must be targeted to the terminal exon of the pre-mRNA. This could reflect a disruption by the 5' end-mutated U1 snRNA of the definition of the terminal exon as described by the exon definition model.
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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.