Regulation of Alternative Splicing in Vivo by Overexpression of Antagonistic Splicing Factors

作者：Javier F. Cáceres, Stefan Stamm, David M. Helfman, Adrian R. Krainer · 发表于：Science · 年份：1994 · DOI：10.1126/science.8085156 · 被引用次数：620 · 研究领域：RNA Research and Splicing、RNA Interference and Gene Delivery、RNA and protein synthesis mechanisms

The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or hnRNP A1 complementary DNAs were transiently overexpressed in HeLa cells, and the effect on alternative splicing of several cotransfected reporter genes was measured. Increased expression of SF2/ASF activated proximal 5' splice sites, promoted inclusion of a neuron-specific exon, and prevented abnormal exon skipping. Increased expression of hnRNP A1 activated distal 5' splice sites. Therefore, variations in the intracellular levels of antagonistic splicing factors influence different modes of alternative splicing in vivo and may be a natural mechanism for tissue-specific or developmental regulation of gene expression.