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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.

项目摘要转录后基因调控已经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。我们有大量的初步数据表明，细胞质Rbfox1抑制了在其3 '端含有（U）GCAUG元件的特定靶mRNA的翻译生殖细胞包囊分化的特定阶段的UTR。通过这项提案，我们试图描述细胞质Rbfox1调节的详细机制，生殖细胞囊肿发育过程中阶段特异性mRNA翻译程序。我们一般的策略是（1）确定什么机制控制独特的蛋白质 Rbfox1在生殖细胞包囊中期的表达模式分化，减数分裂开始之前，（2）表征Rbfox 1如何分子调节mRNA靶点的翻译，以实现阶段特异性翻译，抑制和（3）表征Rbfox1如何调节特定的mRNA，生殖细胞发育的步骤，如pumilio和性致死，并确定这些靶点的异位表达在多大程度上有助于Rbfox1突变表型我们预计，这些努力将提供关键的见解，翻译控制层次，促进生殖细胞的发展，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.