NOVEL EXON CONNECTIONS OF THE BRAIN-SPECIFIC (BS) EXON OF THE ADENOMATOUS POLYPOSIS-COLI GENE

Expression of the adenomatous polyposis coil (APC) gene derived exon B S (e.g., brain-specific exon) has been analyzed by RT-PCR, Four novel APC mRNA isoforms derived from alternative splicing of exons 1A, BS an d 1 were identified, which were ubiquitously expressed. One novel cDNA was characterized by cloning and DNA sequence analysis, which combine d the exon 1A (identical with exon 0.3) 3' end with nucleotide positio n +101 of intron 1A and continued throughout exon BS, A second cDNA is oform was isolated, which joined the 3' end of exon 1A with nucleotide position +118 of exon BS. Both novel isoforms were found to be expres sed together with a third novel APC exon connection, which was specifi ed by exon BS/2 joining, This interesting exon junction resulted in no vel deduced amino terminal open reading frames, which are completely i n-frame with sequences located further downstream, Systematic exon con nection analyses revealed that APC transcripts with exon BS/2 junction s were predominantly detected with a fixed exon composition. RT-PCR an alyses did not identify facultative skipping of exons 9, 10A and 14 in this type of mRNA, in contrast to exon 1-containing APC transcripts a nalyzed from the same cDNA pool under identical conditions, Hence, exo n 1 skipping of exon BS-positive mRNA molecules might preferentially e ncode unique APC polypeptide chains, which are characterized by an alt ernative amino terminus and extended heptad repeat structures due to c ombined incorporation of exons 9 and 10A. (C) 1997 Wiley-Liss, Inc.