Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA.

Abstract

Poly(A)+ RNA, isolated from a single 7-mo fetal human aorta, was used to synthesize cDNA by the RNase H method, and the cDNA was inserted into XgtlO. Recombinant phage containing elastin sequences were identified by hybridization with cloned, exon-containing fragments of the human elastin gene. Three clones containing inserts of 3.3, 2.7, and 2.3 kilobases were selected for further analysis. Three overlapping clones containing 17.8 kilobases of the human elastin gene were also isolated from genomic libraries. Complete sequence analysis of the six clones demonstrated that: (i) the cDNA encompassed the entire translated portion of the mRNA encoding 786 amino acids, including several unusual hydrophilic amino acid sequences not previously identified in porcine tropoelastin, (it) exons encoding either hydrophobic or crosslinking domains in the protein alternated in the gene, and (Wil) a great abundance of Alu repetitive sequences occurred throughout the introns. The data also indicated substantial alternative splicing of the mRNA. These results suggest the potential for significant variation in the precise molecular structure of the elastic fiber in the human population.

Supramolecular Amyloid-like Assembly of the Polypeptide Sequence Coded by Exon 30 of Human Tropoelastin

“…In the alternate succession of hydrophobic and cross-linking domains, peculiar of tropoelastin (27), this peptide belongs to the C-terminal hydrophobic domains of human tropoelastin and has been indicated as fundamental for a correct assembly of elastin (10). It is a glycine-rich domain, containing 13 glycine residues up to 25 residues, and contains only hydrophobic residues.…”

Elastin: mutational spectrum in supravalvular aortic stenosis

“…Three occur in exons reported to be spliced out in vivo (exons 13, 26 and 30). 20,21 Alternative splicing-out of a proportion of these mutated exons should result in some degree of phenotypic rescue; however, all three patients had severe SVAS. One explanation could be that the missense mutations activate cryptic splice sites that induce additional splicing out of that exon.…”

Elastin structure and its involvement in skin photoageing

“…As a result of alternative splicing, different isoforms of the soluble tropoelastin protein have previously been identified, suggesting a potential regulatory mechanism in the expression of this gene. It is known that different tropoelastin isoforms may affect the physical properties of fibres due to changes in the domains in which crosslinking should occur [37,38,61].…”