Different mechanisms are responsible for the low accumulation of transcripts from intronless and 3' splice site deleted genes.

A large reduction in the accumulation of mouse beta-globin mRNA occurs when both introns are deleted from its gene. This reduction is ameliorated if a sequence from HSV-1 thymidine kinase (TK), a naturally intronless gene, is inserted into the intronless globin construct. A large reduction in globin mRNA accumulation also occurs when just the terminal 3' splice site region is deleted. This reduction is not ameliorated by the insertion of TK sequence. Different mechanisms therefore must be responsible for the reduced accumulation of mRNA from the intronless and 3' splice site deleted genes. The ability of TK sequence to enhance mRNA accumulation was dependent on its position within the intronless construct. Data are consistent with a model in which pre-mRNAs are co-transcriptionally channelled into intron-dependent or intron-independent metabolic pathways.