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Article: A 5' splice site mutation affecting the pre-mRNA splicing of two upstream exons in the collagen COL1A1 gene. Exon 8 skipping and altered definition of exon 7 generates truncated proα1(I) chains with a non-collagenous insertion destabilizing the triple helix

TitleA 5' splice site mutation affecting the pre-mRNA splicing of two upstream exons in the collagen COL1A1 gene. Exon 8 skipping and altered definition of exon 7 generates truncated proα1(I) chains with a non-collagenous insertion destabilizing the triple helix
Authors
Issue Date1994
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 1994, v. 302 n. 3, p. 729-735 How to Cite?
AbstractA heterozygous de novo G to A point mutation in intron 8 at the + 5 position of the splice donor site of the gene for the proα1(I) chain of type I procollagen, COL1A1, was defined in a patient with type IV osteogenesis imperfecta. The splice donor site mutation resulted not only in the skipping of the upstream exon 8 but also unexpectedly had the secondary effect of activating a cryptic splice site in the next upstream intron, intron 7, leading to re-definition of the 3' limit of exon 7. These pre-mRNA splicing aberrations cause the deletion of exon 8 sequences from the mature mRNA and the inclusion of 96 bp of intron 7 sequence. Since the mis-splicing of the mutant allele product resulted in the maintenance of the correct codon reading frame, the resultant proα1(I) chain contained a short non-collagenous 32-amino-acid sequence insertion within the repetitive Gly-Xaa-Yaa collagen sequence motif. At the protein level, the mutant α1(I) chain was revealed by digestion with pepsin, which cleaved the mutant procollagen within the protease-sensitive non-collagenous insertion, producing a truncated α1(I). This protease sensitivity demonstrated the structural distortion to the helical structure caused by the insertion. In long-term culture with ascorbic acid, which stimulates the formation of a mature crosslinked collagen matrix, and in tissues, there was no evidence of the mutant chain, suggesting that during matrix formation the mutant chain was unable to be stably incorporated into the matrix and was degraded proteolytically.
Persistent Identifierhttp://hdl.handle.net/10722/147387
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBateman, JFen_US
dc.contributor.authorChan, Den_US
dc.contributor.authorMoeller, Ien_US
dc.contributor.authorHannagan, Men_US
dc.contributor.authorCole, WGen_US
dc.date.accessioned2012-05-29T06:03:21Z-
dc.date.available2012-05-29T06:03:21Z-
dc.date.issued1994en_US
dc.identifier.citationBiochemical Journal, 1994, v. 302 n. 3, p. 729-735en_US
dc.identifier.issn0264-6021en_US
dc.identifier.urihttp://hdl.handle.net/10722/147387-
dc.description.abstractA heterozygous de novo G to A point mutation in intron 8 at the + 5 position of the splice donor site of the gene for the proα1(I) chain of type I procollagen, COL1A1, was defined in a patient with type IV osteogenesis imperfecta. The splice donor site mutation resulted not only in the skipping of the upstream exon 8 but also unexpectedly had the secondary effect of activating a cryptic splice site in the next upstream intron, intron 7, leading to re-definition of the 3' limit of exon 7. These pre-mRNA splicing aberrations cause the deletion of exon 8 sequences from the mature mRNA and the inclusion of 96 bp of intron 7 sequence. Since the mis-splicing of the mutant allele product resulted in the maintenance of the correct codon reading frame, the resultant proα1(I) chain contained a short non-collagenous 32-amino-acid sequence insertion within the repetitive Gly-Xaa-Yaa collagen sequence motif. At the protein level, the mutant α1(I) chain was revealed by digestion with pepsin, which cleaved the mutant procollagen within the protease-sensitive non-collagenous insertion, producing a truncated α1(I). This protease sensitivity demonstrated the structural distortion to the helical structure caused by the insertion. In long-term culture with ascorbic acid, which stimulates the formation of a mature crosslinked collagen matrix, and in tissues, there was no evidence of the mutant chain, suggesting that during matrix formation the mutant chain was unable to be stably incorporated into the matrix and was degraded proteolytically.en_US
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_US
dc.relation.ispartofBiochemical Journalen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCollagen - Chemistry - Genetics - Metabolismen_US
dc.subject.meshDna, Complementary - Chemistry - Geneticsen_US
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_US
dc.subject.meshExonsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFibroblasts - Chemistryen_US
dc.subject.meshHumansen_US
dc.subject.meshIntronsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshOsteogenesis Imperfecta - Geneticsen_US
dc.subject.meshPoint Mutationen_US
dc.subject.meshProcollagen - Chemistry - Geneticsen_US
dc.subject.meshProtein Denaturationen_US
dc.subject.meshRna Splicing - Geneticsen_US
dc.subject.meshRna, Messenger - Genetics - Metabolismen_US
dc.subject.meshSkin - Chemistryen_US
dc.subject.meshTemperatureen_US
dc.titleA 5' splice site mutation affecting the pre-mRNA splicing of two upstream exons in the collagen COL1A1 gene. Exon 8 skipping and altered definition of exon 7 generates truncated proα1(I) chains with a non-collagenous insertion destabilizing the triple helixen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7945197-
dc.identifier.scopuseid_2-s2.0-0027937274en_US
dc.identifier.volume302en_US
dc.identifier.issue3en_US
dc.identifier.spage729en_US
dc.identifier.epage735en_US
dc.identifier.isiWOS:A1994PJ33700015-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridBateman, JF=16135557700en_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridMoeller, I=7004124283en_US
dc.identifier.scopusauthoridHannagan, M=6507095190en_US
dc.identifier.scopusauthoridCole, WG=7201518727en_US

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