Exon/intron structure and alternative transcripts of the CUTL1 gene

The human CUTL1 gene (Cut-like 1) is a candidate tumor suppressor gene located on chromosome 7 at band 22, a region that is frequently deleted in several human cancers. The gene spans at least 340kb and contains 33 exons. Synthesis of five different transcripts involves two promoter regions, two polyadenylation sites and seven alternative splicing events. The two polyadenylation sites are located at the ends of exons 24 and 33 and are separated by approximately 40kb. Transcription is initiated in two genomic regions, giving rise to alternate first exons which are spliced to a common exon 2. All transcripts contain exons 2 to 14, but differ in their 3' regions. Exon 14 can be spliced alternatively to the beginning or the middle of exon 15, or to exon 25, generating transcripts with exons 15 to 24 or exons 25 to 33. Moreover, exon 16 can be spliced out from the mature transcripts that contain exons 15 to 24. Overall, five distinct transcripts are generated as a result of alternative transcription initiation, splicing and polyadenylation. We discuss potential mechanisms by which alternate polyadenylation site usage may affect alternative splicing events and vice versa.