A critical genetic interaction between Gemin3/Ddx20 and translation initiation factor NAT1/eIF4G2 drives development

IF 2.5 3区生物学 Q2 DEVELOPMENTAL BIOLOGY

Developmental biology Pub Date : 2025-02-07 DOI:10.1016/j.ydbio.2025.02.003

Rebecca Cacciottolo , Ruben J. Cauchi

{"title":"A critical genetic interaction between Gemin3/Ddx20 and translation initiation factor NAT1/eIF4G2 drives development","authors":"Rebecca Cacciottolo , Ruben J. Cauchi","doi":"10.1016/j.ydbio.2025.02.003","DOIUrl":null,"url":null,"abstract":"<div><div>Gemin3 (Gem3) or DEAD-box RNA helicase 20 (Ddx20) has been mostly implicated in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) as part of the SMN-Gemins complex. Nonetheless, several studies have hinted at its participation in diverse snRNP-independent activities. Here, we utilised a narrow unbiased genetic screen to discover novel Gem3 interactors in Drosophila with the aim of gaining better insights on its function in vivo. Through this approach, we identified a novel genetic interaction between Gem3 and NAT1, which encodes the Drosophila orthologue of translational regulator eIF4G2. Despite lack of a physical association, loss of NAT1 function was found to downregulate Gem3 mRNA levels. Extensive convergence in transcriptome alterations downstream of Gem3 and NAT1 silencing further supports a functional relationship between these factors in addition to showing a requirement for both in actin cytoskeleton organisation and organism development, particularly neurodevelopment. In confirmation, flies with either Gem3 or NAT1 depletion exhibited brain growth defects and reduced muscle contraction. Severe delays in developmental progression were also observed in a newly generated Gem3 hypomorphic mutant. Our data linking Gemin3 to a key component of the translational machinery support an emerging role for Gemin3 in translation that is also critical during organism development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"521 ","pages":"Pages 37-51"},"PeriodicalIF":2.5000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0012160625000338","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Gemin3 (Gem3) or DEAD-box RNA helicase 20 (Ddx20) has been mostly implicated in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) as part of the SMN-Gemins complex. Nonetheless, several studies have hinted at its participation in diverse snRNP-independent activities. Here, we utilised a narrow unbiased genetic screen to discover novel Gem3 interactors in Drosophila with the aim of gaining better insights on its function in vivo. Through this approach, we identified a novel genetic interaction between Gem3 and NAT1, which encodes the Drosophila orthologue of translational regulator eIF4G2. Despite lack of a physical association, loss of NAT1 function was found to downregulate Gem3 mRNA levels. Extensive convergence in transcriptome alterations downstream of Gem3 and NAT1 silencing further supports a functional relationship between these factors in addition to showing a requirement for both in actin cytoskeleton organisation and organism development, particularly neurodevelopment. In confirmation, flies with either Gem3 or NAT1 depletion exhibited brain growth defects and reduced muscle contraction. Severe delays in developmental progression were also observed in a newly generated Gem3 hypomorphic mutant. Our data linking Gemin3 to a key component of the translational machinery support an emerging role for Gemin3 in translation that is also critical during organism development.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Developmental biology 生物-发育生物学

CiteScore

5.30

自引率

3.70%

发文量

182

审稿时长

1.5 months

期刊介绍： Developmental Biology (DB) publishes original research on mechanisms of development, differentiation, and growth in animals and plants at the molecular, cellular, genetic and evolutionary levels. Areas of particular emphasis include transcriptional control mechanisms, embryonic patterning, cell-cell interactions, growth factors and signal transduction, and regulatory hierarchies in developing plants and animals.