上游开放阅读框动态调节CLOCK蛋白翻译,调节昼夜节律和睡眠。

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2025-05-12 eCollection Date: 2025-05-01 DOI:10.1371/journal.pbio.3003173
Yuanqiang Sun, Ke Shui, Qinyu Li, Chenlu Liu, Wanting Jin, Jian-Quan Ni, Jian Lu, Luoying Zhang
{"title":"上游开放阅读框动态调节CLOCK蛋白翻译,调节昼夜节律和睡眠。","authors":"Yuanqiang Sun, Ke Shui, Qinyu Li, Chenlu Liu, Wanting Jin, Jian-Quan Ni, Jian Lu, Luoying Zhang","doi":"10.1371/journal.pbio.3003173","DOIUrl":null,"url":null,"abstract":"<p><p>The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in Drosophila circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock (Clk), rhythmically and substantially attenuate CLK protein translation in Drosophila, with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs leads to increased CLK protein levels during the day and results in a shortened circadian cycle, along with a broad shift in clock gene expression rhythms. Notably, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to seasonal daylight variations. Furthermore, the Clk uORFs act as an important regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003173"},"PeriodicalIF":9.8000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121920/pdf/","citationCount":"0","resultStr":"{\"title\":\"Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep.\",\"authors\":\"Yuanqiang Sun, Ke Shui, Qinyu Li, Chenlu Liu, Wanting Jin, Jian-Quan Ni, Jian Lu, Luoying Zhang\",\"doi\":\"10.1371/journal.pbio.3003173\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in Drosophila circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock (Clk), rhythmically and substantially attenuate CLK protein translation in Drosophila, with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs leads to increased CLK protein levels during the day and results in a shortened circadian cycle, along with a broad shift in clock gene expression rhythms. Notably, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to seasonal daylight variations. Furthermore, the Clk uORFs act as an important regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.</p>\",\"PeriodicalId\":49001,\"journal\":{\"name\":\"PLoS Biology\",\"volume\":\"23 5\",\"pages\":\"e3003173\"},\"PeriodicalIF\":9.8000,\"publicationDate\":\"2025-05-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121920/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PLoS Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1371/journal.pbio.3003173\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"Agricultural and Biological Sciences\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pbio.3003173","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 0

摘要

昼夜节律是一种进化上保守的机制,翻译调节越来越被认为是其调节的关键。在这项研究中,我们发现上游开放阅读框架(uorf)在果蝇昼夜节律基因中富集,在核心昼夜节律基因中存在特别保守的uorf。我们证明了核心时钟基因clock (Clk)的uorf在果蝇中有节律地和实质性地减弱了Clk蛋白的翻译,在白天发生明显的抑制。消除Clk uORFs导致白天Clk蛋白水平升高,导致昼夜周期缩短,同时时钟基因表达节律发生广泛变化。值得注意的是,Clk - uORF的缺失也通过减少多巴胺能活动来增加早晨睡眠。除了日常的昼夜节律调节外,Clk uorf还在调节睡眠模式以应对季节性日光变化方面发挥作用。此外,Clk uorf作为一个重要的调节因子,塑造大量基因的节律性表达,并影响多方面的生理结果。总的来说,我们的研究揭示了uorf动态调整下游编码序列以适应环境变化的复杂方式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep.

The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in Drosophila circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock (Clk), rhythmically and substantially attenuate CLK protein translation in Drosophila, with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs leads to increased CLK protein levels during the day and results in a shortened circadian cycle, along with a broad shift in clock gene expression rhythms. Notably, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to seasonal daylight variations. Furthermore, the Clk uORFs act as an important regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信