title: Defective splicing induced by 4NQO in the hamster hprt gene.
abstract: The molecular analysis of mutations affecting mRNA processing may contribute to a better understanding of the splicing mechanism through the identification of genomic sequences necessary for the recognition of splice sites. In this paper we report the sequence analysis of 14 splice mutants induced by 4-nitroquinoline 1-oxide (4NQO) at the hamster hypoxanthine-guanine-phosphoribosyltransferase (hprt) locus. We show that mutations at the 3' acceptor splice site or at the first or fifth base of the 5' donor splice site are responsible for exon skipping. In addition, mutations in exon sequences also determine the skipping of one or more exons. Our data indicate that point mutations in intron regions at either side of an internal exon may induce the skipping of the same exon, supporting a model where the exon is the unit of early spliceosome assembly. Furthermore, they suggest that the splicing of hprt mRNA precursors may proceed through a clustering of exons 2, 3 and 4 which are then spliced in a concerted way.
authors.affiliation: Laboratory of Mutagenesis, IST, National Institute for Research on Cancer, CSTA, Genoa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Menichini
authors.forename: A
authors.initials: A
authors.lastname: Inga
authors.forename: G
authors.initials: G
authors.lastname: Fronza
authors.forename: R
authors.initials: R
authors.lastname: Iannone
authors.forename: P
authors.initials: P
authors.lastname: Degan
authors.forename: P
authors.initials: P
authors.lastname: Campomenosi
authors.forename: A
authors.initials: A
authors.lastname: Abbondandolo
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000187:drug effects*
chemical_list: D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase