Article abstract
Nature Genetics 40, 1416 - 1425 (2008)
Published online: 2 November 2008 | doi:10.1038/ng.264
Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines
John C Castle1, Chaolin Zhang2, Jyoti K Shah1, Amit V Kulkarni1, Auinash Kalsotra3, Thomas A Cooper3,4 & Jason M Johnson1
Abstract
Alternative pre–messenger RNA splicing influences development, physiology and disease, but its regulation in humans is not well understood, partially because of the limited scale at 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 seem 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%.
- Rosetta Inpharmatics LLC, Seattle, Washington 98109, USA.
- Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
- Departments of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
- Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Correspondence to: John C Castle1 e-mail: john_castle@merck.com
Correspondence to: Jason M Johnson1 e-mail: jason_johnson@merck.com
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
RNA-binding proteins switch gears to drive alternative splicing in neuronsNature Structural & Molecular Biology News and Views (01 Jul 2007)
RESEARCH
A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUGThe EMBO Journal Article (17 Feb 2003)
Alternative isoform regulation in human tissue transcriptomesNature Article (27 Nov 2008)
Molecular basis of RNA recognition by the human alternative splicing factor Fox-1The EMBO Journal Article (11 Jan 2006)
See all 21 matches for Research
