Aberrant splicing of an alternative exon in the Drosophila troponin-T gene affects flight muscle development.
During myofibrillogenesis, many muscle structural proteins assemble to form the highly ordered contractile sarcomere. Mutations in these proteins can lead to dysfunctional muscle and various myopathies. We have analyzed the Drosophila melanogaster troponin T (TnT) up1 mutant that specifically affects the indirect flight muscles (IFM) to explore troponin function during myofibrillogenesis. The up1 muscles lack normal sarcomeres and contain "zebra bodies," a phenotypic feature of human nemaline myopathies. We show that the up(1) mutation causes defective splicing of a newly identified alternative TnT exon (10a) that encodes part of the TnT C terminus. This exon is used to generate a TnT isoform specific to the IFM and jump muscles, which during IFM development replaces the exon 10b isoform. Functional differences between the 10a and 10b TnT isoforms may be due to different potential phosphorylation sites, none of which correspond to known phosphorylation sites in human cardiac TnT. The absence of TnT mRNA in up1 IFM reduces mRNA levels of an IFM-specific troponin I (TnI) isoform, but not actin, tropomyosin, or troponin C, suggesting a mechanism controlling expression of TnT and TnI genes may exist that must be examined in the context of human myopathies caused by mutations of these thin filament proteins.
Nongthomba
Upendra
U
Department of Biology, University of York, York, YO10 5DD, United Kingdom.
Ansari
Maqsood
M
Thimmaiya
Divesh
D
Stark
Meg
M
Sparrow
John
J
D017398:Alternative Splicing; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D009119:Muscle Contraction / Q000235:genetics; D024510:Muscle Development / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009218:Myosins / Q000235:genetics; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure; D020107:Troponin T / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development* / Q000648:ultrastructure
D029721:Drosophila Proteins; D020107:Troponin T; D009218:Myosins