ArticleMolecular and cellular biology2000
Human genomic sequences that inhibit splicing.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- A New Class of Pathogenic Non-Coding Variants in GLA.International journal of molecular sciences · 2026Article
- Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4.Nature structural & molecular biology · 2025Article
- A Comprehensive Analysis of the Alternative Splicing Co-Factor U2AF65B Gene Family Reveals Its Role in Stress Responses and Root Development.International journal of molecular sciences · 2025Article
- Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing.Genome research · 2025Article
- Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing.bioRxiv : the preprint server for biology · 2024Article
- Exonic splicing code and coordination of divalent metals in proteins.Nucleic acids research · 2024Article
- Pre-mRNA splicing order is predetermined and maintains splicing fidelity across multi-intronic transcripts.Nature structural & molecular biology · 2023Article
- Exonic splicing code and protein binding sites for calcium.Nucleic acids research · 2022Article
- Transposon clusters as substrates for aberrant splice-site activation.RNA biology · 2021Article
- Evaluation of both exonic and intronic variants for effects on RNA splicing allows for accurate assessment of the effectiveness of precision therapies.PLoS genetics · 2020Article
- Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation.Journal of clinical immunology · 2020Article
- Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4.Human mutation · 2019Article
- A birth of bipartite exon by intragenic deletion.Molecular genetics & genomic medicine · 2017Article
- Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The role of short RNA loops in recognition of a single-hairpin exon derived from a mammalian-wide interspersed repeat.RNA biology · 2015Article
- Selection on synonymous codons in mammalian rhodopsins: a possible role in optimizing translational processes.BMC evolutionary biology · 2014Article
- Role of VEGF-C gene polymorphisms in susceptibility to hepatocellular carcinoma and its pathological development.Journal of clinical laboratory analysis · 2014Article
- Systematical identification of splicing regulatory cis-elements and cognate trans-factors.Methods (San Diego, Calif.) · 2014Article
- Article
- Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.BMC molecular biology · 2013Article
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2 authors.
Funding
Abstract
Mammalian genes are characterized by relatively small exons surrounded by variable lengths of intronic sequence. Sequences similar to the splice signals that define the 5' and 3' boundaries of these exons are also present in abundance throughout the surrounding introns. What causes the real sites to be distinguished from the multitude of pseudosites in pre-mRNA is unclear. Much progress has been made in defining additional sequence elements that enhance the use of particular sites. Less work has been done on sequences that repress the use of particular splice sites. To find additional examples of sequences that inhibit splicing, we searched human genomic DNA libraries for sequences that would inhibit the inclusion of a constitutively spliced exon. Genetic selection experiments suggested that such sequences were common, and we subsequently tested randomly chosen restriction fragments of about 100 bp. When inserted into the central exon of a three-exon minigene, about one in three inhibited inclusion, revealing a high frequency of inhibitory elements in human DNA. In contrast, only 1 in 27 Escherichia coli DNA fragments was inhibitory. Several previously identified silencing elements derived from alternatively spliced exons functioned weakly in this constitutively spliced exon. In contrast, a high-affinity site for U2AF65 strongly inhibited exon inclusion. Together, our results suggest that splicing occurs in a background of repression and, since many of our inhibitors contain splice like signals, we suggest that repression of some pseudosites may occur through an inhibitory arrangement of these sites.
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