Unusual misregulation of RNA splicing caused by insertion of a transposable element into the T (Brachyury) locus

Abstract

Background: The TWis mutant allele of the Brachyury, or T, gene was created by insertion of an endogenous retrovirus-like early transposon (ETn) element into the exon 7 splice donor consensus sequence of the 8 exon T locus. While the developmental consequences of this disruption have been well characterized, the molecular consequences have not been previously investigated, and it has been assumed that the insertion results in a truncated protein. This study sought to further characterize the mutant TWis allele by investigating the nature of the transcripts produced by insertion of this transposable element. Results: Using an RT-PCR based approach, we have shown that at least 8 different mutant transcripts are produced from the TWis allele. All TWis transcripts bypass the mutated exon 7 splice donor site, such that wild type T transcripts are not produced from the TWis allele. Conclusions: This result shows an unsuspected misregulation of RNA splicing caused by insertion of a transposable element, that could have more widespread consequences in the genome. © 2003 Goldin and Papaioannou; licensee BioMed Central Ltd.