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Cited by 324

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Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines

Open access
Castle, John C, Zhang, Chaolin, Shah, Jyoti K, Kulkarni, Amit V, Kalsotra, Auinash, Cooper, Thomas A, Johnson, Jason M·2008·Nature Genetics

Abstract

Alternative pre–messenger RNA splicing impacts development, physiology, and disease, but its regulation in humans is not well understood, partially due to the limited scale to which the expression of specific splicing events has been measured. We generated the first genome-scale expression compendium of human alternative splicing events using custom whole-transcript microarrays monitoring expression of 24,426 alternative splicing events in 48 diverse human samples. Over 11,700 genes and 9,500 splicing events were differentially expressed, providing a rich resource for studying splicing regulation. An unbiased, systematic screen of 21,760 4-mer to 7-mer words for cis-regulatory motifs identified 143 RNA 'words' enriched near regulated cassette exons, including six clusters of motifs represented by UCUCU, UGCAUG, UGCU, UGUGU, UUUU, and AGGG, which map to trans-acting regulators PTB, Fox, Muscleblind, CELF/CUG-BP, TIA-1, and hnRNP F/H, respectively. Each cluster showed a distinct pattern of genomic location and tissue specificity. For example, UCUCU occurs 110 to 35 nucleotides preceding cassette exons upregulated in brain and striated muscle but depleted in other tissues. UCUCU and UGCAUG appear to have similar function but independent action, occurring 5' and 3', respectively, of 33% of the cassette exons upregulated in skeletal muscle but co-occurring for only 2%.

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Metadata

Authors
Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A. V., Kalsotra, A., Cooper, T. A., & Johnson, J. M.
Venue
Nature Genetics
Published
2008-11-02
Volume
40
Issue
12
Pages
1416-1425
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W324535036
Cited by
324
References
52
FWCI
13.40
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. https://app.cochat.ai/papers/10.1038/ng.264
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Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A. V., Kalsotra, A., Cooper, T. A., & Johnson, J. M. (2008). Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nature Genetics. https://doi.org/10.1038/ng.264

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