Cited by 1,044RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

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Context-dependent control of alternative splicing by RNA-binding proteins

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Fu, Xiang-Dong, Ares, Manuel·2014·Nature Reviews Genetics

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Abstract

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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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
ORCID: Fu, Xiang-Dong
Ares, Manuel
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2014-08-12
Volume: 15
Issue: 10
Pages: 689-701
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg3778
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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Context-dependent control of alternative splicing by RNA-binding proteins

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