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P granules and control of germ cell development

P颗粒和生殖细胞发育的控制

基本信息

批准号：
10406308
负责人：
Ekaterina Voronina
金额：
$ 29.3万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10406308
关键词：
Address Adult Animal Model Animals Binding Binding Sites Biochemical Biological Models Caenorhabditis elegans Cell physiology Characteristics Cytoplasmic Granules Cytoplasmic Organelle Development Embryo Ensure Fertility Functional disorder Gene Expression Profile Genes Genetic Genetic Translation Germ Germ Cells Human In Vitro Infertility Lead Link Mediating Meiosis Messenger RNA Molecular Mutagenesis Mutate Mutation Nematoda Organelles Organism Peptides Play Post-Transcriptional Regulation Proteins RNA Binding RNA-Binding Proteins Regulation Regulatory Pathway Reproduction Research Role Site Somatic Cell System Testing Translational Regulation Translational Repression Work carcinogenesis cofactor genetic analysis genetic regulatory protein germline stem cells imaging approach in vivo innovation insight mRNA Stability prevent public health relevance recruit reproductive function stem cells tool translational impact

项目摘要

Abstract Germ cells carry out the reproductive function of multicellular organisms, and normal germ cell development ensures survival of the species. Germ granules are conserved cytoplasmic organelles of germ cells, essential for survival, differentiation, and function of these cells. Mutations in germ granule components or loss of their expression lead to infertility in model organisms and are associated with infertility in humans. By contrast, inappropriate expression of germ granule components in somatic cells is linked to carcinogenesis in humans. Many RNA-binding proteins and developmentally regulated mRNAs are found enriched in germ granules, leading to a hypothesis that these organelles function in regulation of mRNA stability or translational activity; yet, the molecular function of these organelles is still undefined. The nematode C. elegans has been instrumental for analysis of mRNA translational control in germline development. Through focusing on cofactors that promote localization of RNA-binding regulatory protein FBF-2 to germ granules (called P granules in this species) in germline stem cells we have generated a set of innovative tools that will address key mechanisms through which P granules regulate FBF-2 activity. By integrating genetic, molecular, biochemical and imaging-based approaches, we will: 1) Determine how FBF-2 interaction with a cofactor protein DLC-1 important for P granule localization impacts translational repression exerted by FBF-2; 2) Define the mechanisms of P granule remodeling that specifically degrade FBF-2 at the onset of meiosis when stem cells transition from proliferation to differentiation; 3) Determine the role of DLC-1 binding to core P granule components in regulation of stability of embryonic P granules and in recruitment of transient P granule components such as FBF-2 to adult germline P granules. Our experimental system is poised to reveal specific molecular mechanisms mediating the interplay between germ granules and translational regulation. Since germ granules are conserved organelles and our research focuses on conserved regulatory proteins, studies in this model system will provide critical insight into the causes of infertility in humans.

摘要

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Caenorhabditis elegans DLC-1 associates with ribonucleoprotein complexes to promote mRNA regulation.

秀丽隐杆线虫 DLC-1 与核糖核蛋白复合物结合以促进 mRNA 调节。

DOI：
10.1002/1873-3468.13259
发表时间：
2018
期刊：
FEBS letters
影响因子：
3.5
作者：
Day,NicholasJ;Ellenbecker,Mary;Voronina,Ekaterina
通讯作者：
Voronina,Ekaterina

DLC-1 facilitates germ granule assembly in Caenorhabditis elegans embryo.

DOI：
10.1091/mbc.e21-05-0275
发表时间：
2022-05-01
期刊：
MOLECULAR BIOLOGY OF THE CELL
影响因子：
3.3
作者：
Day, Nicholas J.;Ellenbecker, Mary;Wang, Xiaobo;Voronina, Ekaterina
通讯作者：
Voronina, Ekaterina

Splicing Machinery Facilitates Post-Transcriptional Regulation by FBFs and Other RNA-Binding Proteins in Caenorhabditis elegans Germline.

剪接机制促进线虫种系中 FBF 和其他 RNA 结合蛋白的转录后调节。

DOI：
10.1534/g3.115.019315
发表时间：
2015
期刊：
G3 (Bethesda, Md.)
影响因子：
0
作者：
Novak,Preston;Wang,Xiaobo;Ellenbecker,Mary;Feilzer,Sara;Voronina,Ekaterina
通讯作者：
Voronina,Ekaterina

mRNAs Hit a Sticky Wicket.

mRNA 击中了粘性三柱门。

DOI：
10.1016/j.devcel.2016.03.018
发表时间：
2016
期刊：
Developmental cell
影响因子：
11.8
作者：
Voronina,Ekaterina
通讯作者：
Voronina,Ekaterina

Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells.

动力蛋白轻链 DLC-1 促进 PUF 蛋白 FBF-2 在种系祖细胞中的定位和功能。

DOI：
10.1242/dev.140921
发表时间：
2016
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
Wang,Xiaobo;Olson,JenessaR;Rasoloson,Dominique;Ellenbecker,Mary;Bailey,Jessica;Voronina,Ekaterina
通讯作者：
Voronina,Ekaterina