OSCR

<i>Mettl5</i> coordinates protein production and degradation of PERIOD to regulate sleep in <i>Drosophila</i>.

Overview

Authors: Xiaoyu Wu1, Xingzhuo Yang1, Tiantian Fu1, Yikang Rong2, Juan Du1
ORCID iDs: Xiaoyu Wu, Xingzhuo Yang, Juan Du
  1. 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 Beijing China
  2. MOE Key Lab of Rare Pediatric Diseases, Hengyang College of Medicine, University of South China Hengyang China
Institutions: China Agricultural University (China); University of South China (China)
Journal: eLife, volume 14, article RP103427
Dates: published online 8 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.103427 · PMID 42100920 · PMCID PMC13155753 · OpenAlex W4406463582
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: drosophila (organism), cellular / molecular (subfield)
Methods: Statistics
Keywords: Mettl5, rRNA methyltransferase, proteasome, clock genes, sleep, D. melanogaster
MeSH: Drosophila*, Drosophila melanogaster*, Drosophila Proteins*, Methyltransferases*, Period Circadian Proteins*, Protein Biosynthesis*, Sleep*, Animals, Gene Expression Regulation, Mutation, Proteolysis (* major topic)
Journal subjects: Genetics and Genomics
Topic: Circadian rhythm and melatonin (Endocrine and Autonomic Systems, Neuroscience), according to OpenAlex
Funding: National Natural Science Foundation of China (32070492, 32122017)
Citations: not cited yet (Europe PMC); 56 references in the paper

Abstract

Sleep plays a critical role in animal physiology, primarily governed by the brain, and its disruption is prevalent in various brain disorders. 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 Drosophila Mettl5 mutations. Rescue experiments revealed that Mettl5 functions predominantly within neurons and glia marked by Mettl5-Gal4 to regulate sleep. Previous work established that Mettl5 forms a complex with Trmt112 to influence rRNA methylation. Notably, a mutation in Trmt112 recapitulated these sleep disturbances, implicating translational regulation by the Mettl5/Trmt112 complex. Subsequent RNA-seq and Ribo-seq analyses of Mettl51bp 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Data links

Data availability

The RNA-seq and Ribo-seq data from this publication have been deposited to the NCBI bioproject database https://www.ncbi.nlm.nih.gov/bioproject/ and assigned the identifier PRJNA994860.

The following dataset was generated:

YangX 2024RNA-seq and Ribo-seq revealed the downstream events in Mettl5 mutationNCBI BioProjectPRJNA994860

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 5 authors, 6 keywords, 11 MeSH terms, 1 funder, 56 references.

Cite

This paper

Wu, X., Yang, X., Fu, T., Rong, Y., & Du, J. (2026). <i>Mettl5</i> coordinates protein production and degradation of PERIOD to regulate sleep in <i>Drosophila</i>. eLife, 14, RP103427. https://doi.org/10.7554/elife.103427

BibTeX

@article{wu2026lt,
author = {Wu, Xiaoyu and Yang, Xingzhuo and Fu, Tiantian and Rong, Yikang and Du, Juan},
title = {{\<i\>Mettl5\</i\> coordinates protein production and degradation of PERIOD to regulate sleep in \<i\>Drosophila\</i\>}},
journal = {eLife},
year = {2026},
month = may,
volume = {14},
pages = {RP103427},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.103427},
url = {https://doi.org/10.7554/elife.103427},
pmid = {42100920},
pmcid = {PMC13155753}
}

RIS

TY - JOUR
AU - Wu, Xiaoyu
AU - Yang, Xingzhuo
AU - Fu, Tiantian
AU - Rong, Yikang
AU - Du, Juan
TI - <i>Mettl5</i> coordinates protein production and degradation of PERIOD to regulate sleep in <i>Drosophila</i>
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/05/08
VL - 14
SP - RP103427
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.103427
UR - https://doi.org/10.7554/elife.103427
LA - en
ER -

CSL-JSON

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"language": "en",
"issued": {
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