REGULATION OF ALTERNATIVE SPLICING IN-VIVO BY OVEREXPRESSION OF ANTAGONISTIC SPLICING FACTORS

被引:560
作者
CACERES, JF [1 ]
STAMM, S [1 ]
HELFMAN, DM [1 ]
KRAINER, AR [1 ]
机构
[1] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
关键词
D O I
10.1126/science.8085156
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1706 / 1709
页数:4
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