FIGURE 10-13 Exon recognition through cooperative binding of SR proteins and splicing factors to pre-mRNA. The correct 5′ GU and 3′ AG splice sites are recognized by splicing factors on the basis of their proximity to exons. The exons contain exonic splicing enhancers (ESEs) that are binding sites for SR proteins. When bound to ESEs, the SR proteins interact with one another and promote the cooperative binding of the U1 snRNP to the 5′ splice site of the downstream intron, SF1 and then the U2 snRNP to the branch point of the upstream intron, the 65- and 35-kDa subunits of U2AF to the polypyrimidine tract and AG 3′ splice site of the upstream intron, and other splicing factors (not shown). The resulting RNA-protein cross-exon recognition complex spans an exon and activates the correct splice sites for RNA splicing. Note that the U1 and U2 snRNPs in this unit do not become part of the same spliceosome. The U2 snRNP on the right forms a spliceosome with the U1 snRNP bound to the 5′ end of the same intron. The U1 snRNP shown on the right forms a spliceosome with the U2 snRNP bound to the branch point of the downstream intron (not shown), and the U2 snRNP on the left forms a spliceosome with a U1 snRNP bound to the 5′ splice site of the upstream intron (not shown). Double-headed arrows indicate protein-protein interactions. See T. Maniatis, 2002, Nature 418:236; see also S. M. Berget, 1995, J. Biol. Chem. 270:2411.