The evolutionarily conserved RNA binding protein SMOOTH is essential for maintaining normal muscle function.
The Drosophila smooth gene encodes an RNA binding protein that has been well conserved through evolution. To investigate the pleiotropic functions mediated by the smooth gene, we have selected and characterized two sm mutants, which are viable as adults yet display robust phenotypes (including a significant decrease in lifespan). Utilizing these mutants, we have made the novel observation that disruption of the smooth/CG9218 locus leads to age-dependent muscle degeneration, and motor dysfunction. Histological characterization of adult sm mutants revealed marked abnormalities in the major thoracic tubular muscle: the tergal depressor of the trochanter (TDT). Corresponding defects include extensive loss/disruption of striations and nuclei. These pathological changes are recapitulated in flies that express a smooth RNA interference construct (sm RNAi) in the mesoderm. In contrast, targeting sm RNAi constructs to motor neurons does not alter muscle morphology. In addition to examining the TDT phenotype, we explored whether other muscular abnormalities were evident. Utilizing physiological assays developed in the laboratory, we have found that the thoracic muscle defect is preceded by dysmotility of the gastrointestinal tract. SMOOTH thus joins a growing list of hnRNPs that have previously been linked to muscle physiology/pathophysiology. Our findings in Drosophila set the stage for investigating the role of the corresponding mammalian homolog, hnRNP L, in muscle function.
Draper
Isabelle
I
Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA. idraper@tuftsmedicalcenter.org
Tabaka
Meg E
ME
Jackson
F Rob
FR
Salomon
Robert N
RN
Kopin
Alan S
AS
D000818:Animals; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000502:physiology / Q000503:physiopathology; D040461:Gene Components; D020869:Gene Expression Profiling; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D009132:Muscles / Q000502:physiology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; D029721:Drosophila Proteins; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D016601:RNA-Binding Proteins; C547968:sm protein, Drosophila