Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines.
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%.
Castle
John C
JC
Rosetta Inpharmatics LLC, Seattle, WA 98109, USA.
Zhang
Chaolin
C
Shah
Jyoti K
JK
Kulkarni
Amit V
AV
Kalsotra
Auinash
A
Cooper
Thomas A
TA
Johnson
Jason M
JM
D017398:Alternative Splicing; D002460:Cell Line; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012326:RNA Splicing