Premature termination of transcription and alternative splicing in the human transacylase (E2) gene of the branched-chain alpha-ketoacid dehydrogenase complex.

We have isolated a human genomic clone hgE2-14 containing exons 5, 6, 7 and 8 of the branched-chain alpha-ketoacid dehydrogenase E2 transacylase gene. Sequencing of exon 8 and its surrounding intronic sequences reveals complete identity with the previously reported truncated E2 cDNA (hE2-1) sequence between nucleotides 938 and 1521. We have identified consensus splice site junctions flanking exon 8 and also a cryptic 3' splice site 370 bases upstream from the start of exon 8 in the gene. In addition, two polyadenylation signals located in the hE2-1 cDNA are also present in the intronic sequence downstream of exon 8 which promote termination of transcription. The data indicate that shortened human liver E2 transcripts undergo alternative splicing to yield mRNA of the hE2-1 type.