The DOI matches its Crossref record; 259 of the 259 references it cites were found in a registry or an index.
Mechanisms and Regulation of Alternative Pre-mRNA Splicing
Open accessAbstract
Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional regulation of gene expression, providing significant expansion of the functional proteome of eukaryotic organisms with limited gene numbers. Split eukaryotic genes contain intervening sequences or introns disrupting protein-coding exons, and intron removal occurs by repeated assembly of a large and highly dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear ribonucleoprotein particles, U1, U2, U4/U6, and U5. Biochemical studies over the past 10 years have allowed the isolation as well as compositional, functional, and structural analysis of splicing complexes at distinct stages along the spliceosome cycle. The average human gene contains eight exons and seven introns, producing an average of three or more alternatively spliced mRNA isoforms. Recent high-throughput sequencing studies indicate that 100% of human genes produce at least two alternative mRNA isoforms. Mechanisms of alternative splicing include RNA–protein interactions of splicing factors with regulatory sites termed silencers or enhancers, RNA–RNA base-pairing interactions, or chromatin-based effects that can change or determine splicing patterns. Disease-causing mutations can often occur in splice sites near intron borders or in exonic or intronic RNA regulatory silencer or enhancer elements, as well as in genes that encode splicing factors. Together, these studies provide mechanistic insights into how spliceosome assembly, dynamics, and catalysis occur; how alternative splicing is regulated and evolves; and how splicing can be disrupted by cis- and trans-acting mutations leading to disease states. These findings make the spliceosome an attractive new target for small-molecule, antisense, and genome-editing therapeutic interventions.
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“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 [8]
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“U2 snRNA binds to the branch point during spliceosome assembly and then forms base pairs with the U6 snRNA to become a key portion of the spliceosome catalytic centre for all major class introns6,8,183,184”
From The neurogenetics of alternative splicing (2016) · cites this paper as [8]
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Metadata
- Authors
- Lee, Y., & Rio, D. C.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Rio, Donald C.
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2015-06-02
- Volume
- 84
- Issue
- 1
- Pages
- 291-323
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC4526142
- OpenAlex
- W2153833484
- Cited by
- 1,291
- References
- 259
- Citations by year
- 2026: 82 · 2025: 105 · 2024: 139 · 2023: 142 · 2022: 162 · 2021: 153 · 2020: 127 · 2019: 117 · 2018: 97 · 2017: 90 · 2016: 53 · 2015: 22
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM097352, R01GM104385, P50GM102706, R01GM094890)
- 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, spliceosome, intron removal, RNA-protein interactions, RNA-RNA base pairing, splicing mutation, splicing factor mutations, antisense therapy, genome editing
- MeSH terms
- Animals, Disease, Gene Expression Regulation, Humans, Mutation, RNA Precursors, RNA Splicing, RNA, Catalytic, Spliceosomes, Alternative Splicing, Ribonucleoproteins, Small Nuclear
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