The Role of Evolutionarily Conserved Sequences in Alternative Splicing at the 3' End of Drosophila melanogaster Myosin Heavy Chain RNA

Exon 18 of the muscle myosin heavy chain gene (Mhc) of Drosophila melanogaster is excluded from larval transcripts but included in most adult transcripts. To identify cis-acting elements regulating this alternative RNA splicing, we sequenced the 3' end of Mhc from the distantly related species...

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Bibliographic Details
Published in:Genetics (Austin) 1999-01, Vol.151 (1), p.263-276
Main Authors: Hodges, Dianne, Cripps, Richard M, O'Connor, Martin E, Bernstein, Sanford I
Format: Article
Language:English
Subjects:
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Conserved Sequence
DNA, Complementary
Drosophila - genetics
Drosophila melanogaster
Drosophila melanogaster - genetics
Drosophila virilis
Evolution
Evolution, Molecular
Exons
Gene Expression Regulation
Genes, Insect
Genetics
Insects
Introns
Larva
Molecular Sequence Data
Muscular system
Myosin Heavy Chains - genetics
Pyrimidines
Ribonucleic acid
RNA
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Summary:Exon 18 of the muscle myosin heavy chain gene (Mhc) of Drosophila melanogaster is excluded from larval transcripts but included in most adult transcripts. To identify cis-acting elements regulating this alternative RNA splicing, we sequenced the 3' end of Mhc from the distantly related species D. virilis. Three noncoding regions are conserved: (1) the nonconsensus splice junctions at either end of exon 18; (2) exon 18 itself; and (3) a 30-nucleotide, pyrimidine-rich sequence located about 40 nt upstream of the 3' splice site of exon 18. We generated transgenic flies expressing Mhc mini-genes designed to test the function of these regions. Improvement of both splice sites of adult-specific exon 18 toward the consensus sequence switches the splicing pattern to include exon 18 in all larval transcripts. Thus nonconsensus splice junctions are critical to stage-specific exclusion of this exon. Deletion of nearly all of exon 18 does not affect stage-specific utilization. However, splicing of transcripts lacking the conserved pyrimidine sequence is severely disrupted in adults. Disruption is not rescued by insertion of a different polypyrimidine tract, suggesting that the conserved pyrimidine-rich sequence interacts with tissue-specific splicing factors to activate utilization of the poor splice sites of exon 18 in adult muscle.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1093/genetics/151.1.263