Novel models for RNA splicing that involve a small nuclear RNA

Abstract

Nucleotide sequences of mammalian small nuclear RNAs (snRNAs) have been analyzed with a computer program for complementarity with sequences around a splice junction of various eukaryotic mRNA precursors (pre-mRNAs). A region in U2 RNA or some other snRNAs can form base pairs with both exons surrounding an intron of certain pre-mRNAs and, thereby, can align the two junctions leading to correct splicing of the pre-mRNA. These findings suggest that a snRNA such as U2 can be involved in splicing certain pre-mRNAs by pairing with exons, which we we call an "exon model" for splicing, as compared with the model involving U1 RNA presented by Lerner et al. [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. We constructed a secondary structure model of U1 RNA and studied the capacity of base pairing with pre-mRNAs on the basis of both primary and secondary structures of U1 RNA. We present an alternative model for splicing that involves U1 RNA, which assumes base pairing of noncontiguous regions of U1 RNA with an intron of a pre-mRNA. Pairing of an snRNA with exons could explain correct matching of the two junctions that bound one and the same intron, which is not explained by pairing with consensus sequences at the ends of an intron as proposed by Lerner et al. Pairing of an intron with U1 RNA and pairing of the surrounding exons with another snRNA such as U2 RNA could take place at the same time to insure specificity of splicing.