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

Castle, John C.; Chaolin Zhang; Shah, Jyoti K.; Kulkarni, Amit V.; Kalsotra, Auinash; Cooper, Thomas A; Johnson, Jason M
December 2008
Nature Genetics;Dec2008, Vol. 40 Issue 12, p1416
Academic Journal
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%.


Related Articles

  • Integrating many co-splicing networks to reconstruct splicing regulatory modules. Chao Dai; Wenyuan Li; Juan Liu; Jasmine Zhou, Xianghong // BMC Systems Biology;2012 Supplement 1, Vol. 6 Issue Suppl 1, p1 

    Background: Alternative splicing is a ubiquitous gene regulatory mechanism that dramatically increases the complexity of the protium. However, the mechanism for regulating alternative splicing is poorly understood, and study of coordinated splicing regulation has been limited to individual...

  • ARH: predicting splice variants from genome-wide data with modified entropy. Rasche, Axel; Herwig, Ralf // Bioinformatics;Jan2010, Vol. 26 Issue 1, p84 

    Motivation: Exon arrays allow the quantitative study of alternative splicing (AS) on a genome-wide scale. A variety of splicing prediction methods has been proposed for Affymetrix exon arrays mainly focusing on geometric correlation measures or analysis of variance. In this article, we introduce...

  • New Findings Help Explain Gene Production in The Human Body.  // Nutrition Health Review: The Consumer's Medical Journal;2005, Issue 93, p8 

    The article reports that new findings from researchers at UT-Southwestern Medical Center help explain how the 20,000 to 25,000 genes in the human genome can make the hundreds of thousands of different proteins in bodies. Alternative splicing is a key mechanism for achieving a diverse range of...

  • RNA secondary structure in mutually exclusive splicing. Yun Yang; Leilei Zhan; Wenjing Zhang; Feng Sun; Wenfeng Wang; Nan Tian; Jingpei Bi; Haitao Wang; Dike Shi; Yajian Jiang; Yaozhou Zhang; Yongfeng Jin // Nature Structural & Molecular Biology;Feb2011, Vol. 18 Issue 2, p159 

    Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3ξ pre-mRNA. These elements are...

  • The RNA profile of porcine parvovirus 4, a boca-like virus, is unique among the parvoviruses. Cheung, Andrew; Long, Jin-Xue; Huang, Lv; Yuan, Shi-Shan // Archives of Virology;Nov2011, Vol. 156 Issue 11, p2071 

    PPV4 transcribes its genome from a single promoter, and the RNAs are generated via alternate splicing coupled with alternate polyadenylation, a strategy similar to that of the bocaviruses; however, several differences were detected. The PPV4 ORF1 codes for four NS proteins, while the bocavirus...

  • Genome-wide survey of alternative splicing in the grass Brachypodium distachyon: a emerging model biosystem for plant functional genomics. Sablok, Gaurav; Gupta, P. K.; Baek, Jong-Min; Vazquez, Franck; Xiang Jia Min // Biotechnology Letters;Mar2011, Vol. 33 Issue 3, p629 

    draft sequence of the genome of Brachypodium distachyon, the emerging grass model, was recently released. This represents a unique opportunity to determine its functional diversity compared to the genomes of other model species. Using homology mapping of assembled expressed sequence tags with...

  • Alternative splicing and RNA selection pressure — evolutionary consequences for eukaryotic genomes. Yi Xing; Lee, Christopher // Nature Reviews Genetics;Jul2006, Vol. 7 Issue 7, p499 

    Genome-wide analyses of alternative splicing have established its nearly ubiquitous role in gene regulation in many organisms. Genome sequencing and comparative genomics have made it possible to look in detail at the evolutionary history of specific alternative exons or splice sites, resulting...

  • Gene regulation: Better screening for alternative splicing regulators. Flintoft, Louisa // Nature Reviews Genetics;Jul2013, Vol. 14 Issue 7, p442 

    The article discusses the research on using two complementary minigene reporters to identify the positive and negative splicing regulators of exons.

  • Alternative Splicing: A Potential Source of Functional Innovation in the Eukaryotic Genome. Lu Chen; Tovar-Corona, Jaime M.; Urrutia, Araxi O. // International Journal of Evolutionary Biology;2012, p1 

    Alternative splicing (AS) is a common posttranscriptional process in eukaryotic organisms, by which multiple distinct functional transcripts are produced from a single gene. The release of the human genome draft revealed a much smaller number of genes than anticipated. Because of its potential...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics