Context-dependent control of alternative splicing by RNA-binding proteins
Open accessAbstract
Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control alternative splicing, but it is not yet possible to read the 'splicing code' that dictates splicing regulation on the basis of genome sequence. Each alternative splicing event is controlled by multiple RBPs, the combined action of which creates a distribution of alternatively spliced products in a given cell type. As each cell type expresses a distinct array of RBPs, the interpretation of regulatory information on a given RNA target is exceedingly dependent on the cell type. RBPs also control each other's functions at many levels, including by mutual modulation of their binding activities on specific regulatory RNA elements. In this Review, we describe some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation.
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Alternative splicing patterns are regulated by specialized pre-mRNA binding proteins that alter spliceosome assembly at specific splice sites.
“Alternative splicing patterns (BOX 1) are regulated by specialized pre-mRNA binding proteins that alter spliceosome assembly at specific splice sites5–8”
From The neurogenetics of alternative splicing (2016) · cites this paper as [7]
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- Authors
- Fu, X.-D., & Ares, M.
- Affiliations
- University of California San Diego (US)
- University of California, Santa Cruz (US)
- Corresponding author
- Fu, Xiang-Dong
- Ares, Manuel
- Venue
- Nature Reviews Genetics
- Published
- 2014-08-12
- Volume
- 15
- Issue
- 10
- Pages
- 689-701
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC4440546
- OpenAlex
- W2029979788
- Cited by
- 1,044
- References
- 176
- Citations by year
- 2026: 67 · 2025: 95 · 2024: 89 · 2023: 93 · 2022: 92 · 2021: 99 · 2020: 93 · 2019: 94 · 2018: 93 · 2017: 94 · 2016: 68 · 2015: 61 · 2014: 5
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM052872, GM049369, GM040478, GM052872, R01GM049369, R01GM040478)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- alternative splicing, RNA-binding proteins, splicing regulation, pre-mRNA, combinatorial regulation, cell-type-specific splicing, splicing patterns
- MeSH terms
- Animals, Binding Sites, Humans, Organ Specificity, Protein Binding, RNA-Binding Proteins, Alternative Splicing, Regulatory Elements, Transcriptional, Cellular Microenvironment
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