Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.

Autor: Tallo CA; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614, USA., Duncan LH; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614, USA., Yamamoto AH; The Department of Entomology and Plant Pathology, North Carolina State University, Raleigh, NC 27695-7613, USA., Slaydon JD; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614, USA., Arya GH; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614, USA., Turlapati L; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614, USA., Mackay TFC; The Center for Human Genetics and Department of Genetics and Biochemistry, Clemson University, Greenwood, SC 29646, USA., Carbone MA; The Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27695, USA.; The Center for Integrated Fungal Research and Department of Plant and Microbial Biology, North Carolina State University, Raleigh NC 27695-7244, USA.
Jazyk: angličtina
Zdroj: G3 (Bethesda, Md.) [G3 (Bethesda)] 2021 Jan 18; Vol. 11 (1).
DOI: 10.1093/g3journal/jkaa014
Abstrakt: In cats, mutations in myosin binding protein C (encoded by the MYBPC3 gene) have been associated with hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms linking these mutations to HCM remain unknown. Here, we establish Drosophila melanogaster as a model to understand this connection by generating flies harboring MYBPC3 missense mutations (A31P and R820W) associated with feline HCM. The A31P and R820W flies displayed cardiovascular defects in their heart rates and exercise endurance. We used RNA-seq to determine which processes are misregulated in the presence of mutant MYBPC3 alleles. Transcriptome analysis revealed significant downregulation of genes encoding small nucleolar RNA (snoRNAs) in exercised female flies harboring the mutant alleles compared to flies that harbor the wild-type allele. Other processes that were affected included the unfolded protein response and immune/defense responses. These data show that mutant MYBPC3 proteins have widespread effects on the transcriptome of co-regulated genes. Transcriptionally differentially expressed genes are also candidate genes for future evaluation as genetic modifiers of HCM as well as candidate genes for genotype by exercise environment interaction effects on the manifestation of HCM; in cats as well as humans.
(© The Author(s) 2020. Published by Oxford University Press on behalf of Genetics Society of America.)
Databáze: MEDLINE
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