Regulation of splicing: the importance of being translatable

Abstract

RNA sequences that conform to the consensus sequence of 5' splice sites but are not used for splicing occur frequently in protein coding genes. Mutational analyses have shown that suppression of splicing at such latent sites may be dictated by the necessity to maintain an open reading frame in the mRNA. Here we show that stop codon frequency in introns having latent 5' splice sites is significantly greater than that of introns lacking such sites and significantly greater than the expected occurrence by chance alone. Both observations suggest the occurrence of a general mechanism that recognizes the mRNA reading frame in the context of pre-mRNA.

FIGURE 1.

The occurrence of in-frame stop codons in 100-nt downstream flanks of authentic exons. The line represents the expected occurrence of at least one stop codon by chance alone, using a binomial probability distribution. The parameters were derived from the 2311 sequences in our database: 0.1160 as the probability of an in-frame stop codon in the intron region +1 to +6; 0.0375 as the probability of an in-frame stop codon per triplet in the intron region +7 to +100. (Triangles) observed frequency in introns having latent 5′ splice sites; (circles) observed frequency in introns without latent sites. The X-axis represents the length of segments, in nucleotides, starting from the authentic 5′ splice junction.