Splicing regulators: targets and drugs

摘要

Silencing of splicing regulators by RNA interference, combined with splicing-specific microarrays, has revealed a complex network of distinct alternative splicing events in Drosophila, while a high-throughput screen of more than 6,000 compounds has identified drugs that interfere specifically and directly with one class of splicing regulators in human cells. The importance of splicing in the control of gene expression is underscored by the realization that the human genome codes for far fewer genes than expected [i]: we do not have many more genes than the nematode Caenorhabditis elegans and have fewer than the plant Arabidopsis thaliana. Alternative splicing, whereby regulated splice-site usage results in the generation of different protein isoforms for the same gene locus, is key to multiplying the diversity of proteins produced from the human transcriptome. Computational alignments of transcript data and high-throughput splicing-specific microarray analyses have estimated that as many as 70% ofhuman genes undergo alternative splicing [2,3].