RNA-seq and Ribo-seq revealed the downstream events in Mettl5 mutation
We performed transcriptome and translatome sequencing analysis of the mutant and control groups of CG9666, the homologous gene of human METTL5 in Drosophila melanogaster, to explore the function and regulation mechanism of CG9666 in Drosophila sleep and sleep homeostasis. We used Illumina NovaSeq platform to sequence the RNA and Ribo-seq samples of the two groups of flies, and obtained high-quality data. Differential expression analysis revealed that CG9666 mutant showed significant differences from the control group at both transcriptional and translational levels, indicating that CG9666 might be involved in Drosophila sleep regulation and metabolic adaptation. Further detailed study revealed that the mutation of Mettl5 caused the upregulation of a series of proteasome components through regulating Clock. This study provided new connections and insights into the role of Mettl5, Clock and proteasome in sleep regulation. Mettl5 was previously identified as an rRNA methyltransferase, and is an example of a molecule that functions in both rRNA methylation and proteasome regulation. This study highlighted an integrative role of protein synthesis and degradation in sleep regulation, which may bring new inspiration to the treatment of intellectual disability