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

我们针对黑腹果蝇中人类METTL5的同源基因CG9666的突变体组与对照组，开展了转录组（transcriptome）与翻译组（translatome）测序分析，以探究CG9666在果蝇睡眠及睡眠稳态中的功能与调控机制。本研究采用Illumina NovaSeq测序平台，对两组果蝇的RNA及核糖体测序（Ribo-seq）样本进行测序，最终获得了高质量的测序数据。差异表达分析结果显示，CG9666突变体在转录与翻译水平上均与对照组存在显著差异，提示CG9666可能参与果蝇睡眠调控与代谢适应过程。进一步的深入研究表明，Mettl5突变可通过调控Clock基因，诱导一系列蛋白酶体组分的表达上调。本研究为阐明Mettl5、Clock与蛋白酶体在睡眠调控中的作用机制提供了全新的关联视角与研究见解。此前Mettl5被鉴定为一种核糖体RNA（rRNA）甲基转移酶，本研究也展示了一类可同时参与rRNA甲基化与蛋白酶体调控的分子功能范例。本研究凸显了蛋白质合成与降解过程在睡眠调控中的协同整合作用，或可为智力障碍的临床治疗提供全新的研究灵感。