Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
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.
Cáceres
J F
JF
Cold Spring Harbor Laboratory, NY 11724.
Stamm
S
S
Helfman
D M
DM
Krainer
A R
AR
D017500:Adenovirus E1A Proteins / Q000235:genetics; D017398:Alternative Splicing; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D014162:Transfection; D014335:Tropomyosin / Q000235:genetics
D017500:Adenovirus E1A Proteins; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014335:Tropomyosin; D000068103:Serine-Arginine Splicing Factors