Nucleic Acids Research, 2000, Vol. 28, No. 2 402-410
© 2000 Oxford University Press
An exonic splicing silencer in the testes-specific DNA ligase III ß exon
1Department of Endocrinology, St Bartholomew’s and the Royal London School of Medicine, London EC1A 7BE, UK and 2Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK
Alternative pre-mRNA splicing of two terminal exons (
and ß) regulates the expression of the human DNA ligase III gene. In most tissues, the exon is expressed. In testes and during spermatogenesis, the ß exon is used instead. The exon encodes the interaction domain with a scaffold DNA repair protein, XRCC1, while the ß exon-encoded C-terminal does not. Sequence elements regulating the alternative splicing pattern were mapped by in vitro splicing assays in HeLa nuclear extracts. Deletion of a region beginning in the ß exon and extending into the downstream intron derepressed splicing to the ß exon. Two silencing elements were found within this 101 nt region: a 16 nt exonic splicing silencer immediately upstream of the ß exon polyadenylation signal and a 45 nt intronic splicing silencer. The exonic splicing silencer inhibited splicing, even when the polyadenylation signal was deleted or replaced by a 5' splice site. This element also enhanced polyadenylation under conditions unfavourable to splicing. The splicing silencer partially inhibited assembly of spliceosomal complexes and functioned in an adenoviral pre-mRNA context. Silencing of splicing by the element was associated with cross-linking of a 37 kDa protein to the RNA substrate. The element exerts opposite functions in splicing and polyadenylation.
* To whom correspondence should be addressed at: Department of Endocrinology, St Bartholomew’s and the Royal London School of Medicine, London EC1A 7BE, UK. Tel: +44 171 6018343; Fax: +44 171 6018505; Email: s.l.chew@mds.qmw.ac.uk
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