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Mettl5 is associated with intellectual disability (ID), which often includes sleep disturbances. However, the mechanism underlying these sleep disruptions in ID remains poorly understood. In this study, we investigated the sleep phenotypes resulting from\n                    <jats:italic>Drosophila Mettl5<\/jats:italic>\n                    mutations. Rescue experiments revealed that\n                    <jats:italic>Mettl5<\/jats:italic>\n                    functions predominantly within neurons and glia marked by\n                    <jats:italic>Mettl5<\/jats:italic>\n                    -Gal4 to regulate sleep. Previous work established that Mettl5 forms a complex with Trmt112 to influence rRNA methylation. Notably, a mutation in\n                    <jats:italic>Trmt112<\/jats:italic>\n                    recapitulated these sleep disturbances, implicating translational regulation by the Mettl5\/Trmt112 complex. Subsequent RNA-seq and Ribo-seq analyses of\n                    <jats:italic>\n                      Mettl5\n                      <jats:sup>1bp<\/jats:sup>\n                    <\/jats:italic>\n                    mutants uncovered downstream effects, including altered expression of proteasome components and clock genes. Rescue experiments confirmed that the net increase in PERIOD protein underlies the sleep phenotype. This study illuminates the interplay between ribosome function, clock genes, and the proteasome in sleep regulation, highlighting the integrated roles of protein synthesis and degradation. These findings could potentially provide an example for in vivo study of rRNA methylation function, expand our understanding of protein homeostasis in sleep, and offer insights into the sleep phenotypes associated with ID.\n                  <\/jats:p>","DOI":"10.7554\/elife.103427","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:25:31Z","timestamp":1737026731000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.103427","source":"Crossref","is-referenced-by-count":1,"title":["Mettl5 coordinates protein production and degradation of PERIOD to regulate sleep in Drosophila"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7183-899X","authenticated-orcid":true,"given":"Xiaoyu","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MOA Key Lab of Pest Monitoring and Green Management, Department of Entomology, College of Plant Protection, China Agricultural University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0025-5503","authenticated-orcid":true,"given":"Xingzhuo","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MOA Key Lab of Pest Monitoring and Green Management, Department of Entomology, College of Plant Protection, China Agricultural University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Tiantian","family":"Fu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MOA Key Lab of Pest Monitoring and Green Management, Department of Entomology, College of Plant Protection, China Agricultural University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Yikang","family":"Rong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"MOE Key Lab of Rare Pediatric Diseases, Hengyang College of Medicine, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-3613","authenticated-orcid":true,"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MOA Key Lab of Pest Monitoring and Green Management, Department of Entomology, College of Plant Protection, China Agricultural University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41583-018-0098-9","type":"journal-article","article-title":"Exploring phylogeny to find the function of sleep","volume":"20","author":"Anafi","year":"2019","journal-title":"Nature Reviews. 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