Regulation of mRNA translation during germline cyst differentiation

种系包囊分化过程中 mRNA 翻译的调控

基本信息

批准号：
10080035
负责人：
Michael Buszczak
金额：
$ 32.4万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10080035
关键词：
3&apos Untranslated Regions Alternative Splicing Bioinformatics Biology Cell Differentiation process Cell Nucleus Cell physiology Cells Cyst Cytoplasm Data Development Diagnostic Disease Drosophila genus Ectopic Expression Elements Exhibits Exons Family Family member Female Gene Expression Genes Genetic Transcription Genetic Translation Germ Cells Goals Grant Insecta Malignant Neoplasms Mediating Medical Meiosis Membrane Messenger RNA Modeling Molecular Nuclear Paper Pattern Phenotype Play Post-Transcriptional Regulation Protein Isoforms Protein Region Proteins Publishing RNA Splicing RNA-Binding Proteins Regulation Reproductive Sciences Role Science Seminal Testing Therapeutic Intervention Tissues Trans-Activators Translational Repression Translations Work autism spectrum disorder base cell type cis acting element differential expression fascinate in vivo innovation insight mutant novel programs protein expression sex stem cell biology stem cells tool

项目摘要

Project Summary Post-transcriptional gene regulation has emerged as a critical control mechanism that orchestrates diverse cellular processes during germ cell differentiation. We have extensive preliminary data that demonstrate cytoplasmic Rbfox1 represses the translation of specific target mRNAs that contain (U)GCAUG elements within their 3' UTRs during specific stages of germline cyst differentiation. Through this proposal, we seek to characterize the detailed mechanisms by which cytoplasmic Rbfox1 regulates stage specific mRNA translation programs during germ cell cyst development. Our general strategy is to (1) determine what mechanisms control the unique protein expression pattern of Rbfox1 during the intermediate stages of germline cyst differentiation, prior to the onset of meiosis, (2) characterize how Rbfox1 molecularly regulates the translation of mRNA targets to achieve stage-specific translational repression and (3) characterize how Rbfox1 regulates specific mRNAs that govern early steps of germ cell development, such as pumilio and sex-lethal, and determine the extent to which ectopic expression of these targets contributes to Rbfox1 mutant phenotypes. We anticipate that these efforts will provide key insights into the translational control hierarchies that promote the development of germ cells across species.

项目概要转录后基因调控已成为一种关键的控制机制，在生殖细胞分化过程中协调不同的细胞过程。我们有大量初步数据表明细胞质 Rbfox1 抑制翻译 3' 端含有 (U)GCAUG 元件的特定目标 mRNA 种系囊肿分化特定阶段的 UTR。通过这个提案，我们寻求表征细胞质 Rbfox1 调节的详细机制生殖细胞囊肿发育过程中阶段特定的 mRNA 翻译程序。我们的一般策略是（1）确定控制独特蛋白质的机制 Rbfox1在种系囊肿中期的表达模式减数分裂开始之前的分化，(2) 表征 Rbfox1 分子如何调节 mRNA 靶标的翻译以实现阶段特异性翻译 (3) 表征 Rbfox1 如何调节控制早期的特定 mRNA 生殖细胞发育的步骤，例如 pumilio 和性致死，并确定这些靶标的异位表达对 Rbfox1 突变体的贡献程度表型。我们预计这些努力将为我们提供重要的见解促进生殖细胞发育的翻译控制层次物种。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly.

DOI：
10.1016/j.celrep.2022.110597
发表时间：
2022-03-29
期刊：
CELL REPORTS
影响因子：
8.8
作者：
Ni, Chunyang;Schmitz, Daniel A.;Lee, Jeon;Pawlowski, Krzysztof;Wu, Jun;Buszczak, Michael
通讯作者：
Buszczak, Michael

Inhibition of the de novo pyrimidine biosynthesis pathway limits ribosomal RNA transcription causing nucleolar stress in glioblastoma cells.

DOI：
10.1371/journal.pgen.1009117
发表时间：
2020-11
期刊：
PLoS genetics
影响因子：
4.5
作者：
Lafita-Navarro MC;Venkateswaran N;Kilgore JA;Kanji S;Han J;Barnes S;Williams NS;Buszczak M;Burma S;Conacci-Sorrell M
通讯作者：
Conacci-Sorrell M

The Dynamic Regulation of mRNA Translation and Ribosome Biogenesis During Germ Cell Development and Reproductive Aging.