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PMID: 1373235 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutations which alter splicing in the human hypoxanthine-guanine phosphoribosyltransferase gene.

Nucleic acids research ·Vol. 20 ·No. 6 ·1992-03-25 ·Pages 1201-8

Steingrimsdottir H, Rowley G, Dorado G, Cole J, Lehmann AR

Abstract

A large proportion of mutations at the human hprt locus result in aberrant splicing of the hprt mRNA. We have been able to relate the mutation to the splicing abnormality in 30 of these mutants. Mutations at the splice acceptor sites of introns 4, 6 and 7 result in splicing out of the whole of the downstream exons, whereas in introns 1, 7 or 8 a cryptic site in the downstream exon can be used. Mutations in the donor site of introns 1 and 5 result in the utilisation of cryptic sites further downstream, whereas in the other introns, the upstream exons are spliced out. Our most unexpected findings were mutations in the middle of exons 3 and 8 which resulted in splicing out of these exons in part of the mRNA populations. Our results have enabled us to assess current models of mRNA splicing. They emphasize the importance of the polypyrimidine tract in splice acceptor sites, they support the role of the exon as the unit of assembly for splicing, and they are consistent with a model proposing a stem-loop structure for exon 8 in the hprt mRNA.

Related Genes
hprt
MeSH Terms
Base Sequence Cell Line DNA DNA Mutational Analysis Exons Humans Hypoxanthine Phosphoribosyltransferase/genetics Molecular Sequence Data Mutation Nucleic Acid Conformation Polymerase Chain Reaction RNA/metabolism RNA Splicing/genetics
Chemicals
RNA DNA Hypoxanthine Phosphoribosyltransferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Steingrimsdottir H
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, UK.
Rowley G
Dorado G
Cole J
Lehmann A R
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/20.6.1201
Published
1992-03-25
Pages
1201-8
Language
English
Region
England
NLM ID
0411011
PMCID
PMC312159
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/20.6.1201 PMC Full Text View journal details
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