Genes encoding the KDM5 family of transcriptional regulators are disrupted in individuals with intellectual disability (ID). To understand the link between KDM5 and ID, we characterized five Drosophila strains harboring missense alleles analogous to those observed in patients. These alleles disrupted neuroanatomical development, cognition and other behaviors, and displayed a transcriptional signature characterized by the downregulation of many ribosomal protein genes. A similar transcriptional profile was observed in KDM5C knockout iPSC-induced human glutamatergic neurons, suggesting an evolutionarily conserved role for KDM5 proteins in regulating this class of gene. In Drosophila, reducing KDM5 changed neuronal ribosome composition, lowered the translation efficiency of mRNAs required for mitochondrial function, and altered mitochondrial metabolism. These data highlight the cellular consequences of altered KDM5-regulated transcriptional programs that could contribute to cognitive and behavioral phenotypes. Moreover, they suggest that KDM5 may be part of a broader network of proteins that influence cognition by regulating protein synthesis.
- MeSH
- aktivace transkripce MeSH
- Drosophila melanogaster genetika metabolismus MeSH
- Drosophila genetika metabolismus MeSH
- histondemethylasy metabolismus genetika MeSH
- lidé MeSH
- mentální retardace genetika metabolismus MeSH
- mitochondrie metabolismus genetika MeSH
- neurony * metabolismus MeSH
- proteiny Drosophily * genetika metabolismus MeSH
- proteosyntéza MeSH
- ribozomální proteiny * genetika metabolismus MeSH
- ribozomy metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
