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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:65-70.)
© 1995 American Heart Association, Inc.

Articles

Loss of a Splice Donor Site at a `Skipped Exon' in a Gene Homologous to Apolipoprotein(a) Leads to an mRNA Encoding a Protein Consisting of a Single Kringle Domain

Christopher D. Byrne; Karen Schwartz; Richard M. Lawn

From Falk Cardiovascular Research Center, Stanford University School of Medicine (Calif).

Abstract Apolipoprotein(a) [apo(a)] and plasminogen are located in a gene cluster on chromosome 6 together with two other genes that share highly homologous 5' flanking regions. We have isolated the human liver transcript derived from one of these genes, designated apo(a)-related gene C, that encodes a polypeptide of 132 amino acids composed of a secretion signal and a single kringle domain. Although the gene encodes several additional kringle domains, sequence analysis shows that the second kringle is incomplete in the derived mRNA because it lacks an apparent exon present in the gene. Analysis of genomic sequence shows that the predicted exon at this site lacks a canonical splice donor site. This results in "exon skipping" during maturation of the mRNA, causing a coding frame shift and the presence of premature stop codons.

Key Words: apolipoprotein(a)-related gene C • exon skipping • kringle • apolipoprotein(a) homologue • alternative splicing

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