Characterizing modes of maternal RNA degradation during vertebrate development
脊椎动物发育过程中母体 RNA 降解模式的表征
基本信息
- 批准号:8416476
- 负责人:
- 金额:$ 5.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-01 至 2015-01-31
- 项目状态:已结题
- 来源:
- 关键词:3&apos Untranslated RegionsAmanitinsAnimalsBindingBiological ModelsCategoriesCell physiologyCellsComputing MethodologiesDataDepositionDevelopmentDevelopmental ProcessDiseaseDrosophila genusElementsEmbryoEmbryologyEmbryonic DevelopmentFertilizationGene Expression RegulationGenesGenetic TranscriptionGenomeHomologous GeneIn Situ HybridizationInstructionLaboratoriesLengthLifeMalignant NeoplasmsMapsMaternal Messenger RNAMediatingMessenger RNAMicroRNAsMolecularMothersOrganismPathway interactionsPatternPeptide Signal SequencesPhenotypePlayPoly APolyadenylationProcessPropertyProtein IsoformsProteinsRNARNA DegradationRNA chemical synthesisRegulationRegulatory ElementReporterReporter GenesResolutionRoleSignal TransductionSiteSpecificityStagingStructureTimeTranscriptTranslationsUntranslated RegionsVertebratesWorkXenopusZebrafishbasedevelopmental diseaseegghuman DICER1 proteinin vivomRNA Stabilitymutantnovelprogramsresearch studyzygote
项目摘要
DESCRIPTION (provided by applicant): Early development in all animals depends initially on the maternal contribution of RNAs and proteins, deposited by the mother into the egg. The genome of the zygote is not actively transcribed initially, and all cellular processes including cel division are mediated by these initial maternal factors. At a later stage, the zygotic genome is activated and control switches from maternally contributed factors to newly synthesized zygotic RNAs and proteins. A key step for subsequent development is the destruction of maternal components. While this process has been known for over three decades, the molecular elements required to clear maternal instructions during vertebrate development remain largely unknown. In this proposal, I will investigate the mechanisms of maternal RNA degradation in vertebrates, using zebrafish as a model system. In Aim 1, I will use high throughput sequencing to identify maternally derived transcripts with correlated degradation patterns. I will compare timecourse expression data in wildtype embryos as well as embryos in which de novo transcription and small regulatory RNA synthesis have been inhibited, in order to define transcripts undergoing degradation by specific mechanisms and under specific temporal control. In Aim 2, I will analyze the lengths and sequence content of the 3' untranslated regions (UTRs) of maternal transcripts and look for regulated differences between the 3'UTRs of zygotic transcripts, under the hypothesis that differential regulation and degradation is mediated by these sequences. In Aim 3, I will characterize the discrete regulatory sequence signals present in 3'UTRs that are the determinants of degradation, using a combination of computational methods and reporter gene constructs. I expect that maternal RNAs that are co-degraded should also contain the same sets of signals. Together these aims will elucidate the ways in which RNA transcripts are differentially degraded. Although these processes are especially prominent during development, they are relevant to all living cells, which need to maintain regulated quantities of RNA messages in order to achieve specific phenotypes. Thus, understanding the mechanisms underlying RNA degradation is key to understanding how this process is misregulated in developmental disorders, cancers, and disease.
描述(由申请人提供):所有动物的早期发育最初取决于母体对RNA和蛋白质的贡献,这些RNA和蛋白质由母体沉积到卵中。受精卵的基因组最初并不活跃地转录,并且包括细胞分裂在内的所有细胞过程都由这些初始的母体因子介导。在后期阶段,合子基因组被激活,并控制从母系贡献因子到新合成的合子RNA和蛋白质的转换。随后发展的一个关键步骤是破坏母体成分。虽然这一过程已经知道了三十多年,但在脊椎动物发育过程中清除母体指令所需的分子元件在很大程度上仍然未知。在这个计划中,我将研究在脊椎动物母体RNA降解的机制,使用斑马鱼作为模型系统。在目标1中,我将使用高通量测序来鉴定具有相关降解模式的母体衍生转录物。我将比较野生型胚胎以及从头转录和小调控RNA合成已被抑制的胚胎中的时程表达数据,以确定转录物通过特定机制和特定的时间控制进行降解。在目标2中,我将分析母体转录本3'非翻译区(UTR)的长度和序列内容,并寻找合子转录本3' UTR之间的调节差异,假设差异调节和降解是由这些序列介导的。在目标3中,我将使用计算方法和报告基因构建体的组合来表征作为降解决定因素的3'UTR中存在的离散调控序列信号。我认为共同降解的母体RNA也应该包含相同的信号。这些目标将共同阐明RNA转录物差异降解的方式。虽然这些过程在发育过程中特别突出,但它们与所有活细胞相关,这些活细胞需要维持RNA信息的调节量以实现特定的表型。因此,理解RNA降解的机制是理解这一过程在发育障碍、癌症和疾病中如何被错误调节的关键。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Miler T. S. Lee其他文献
Miler T. S. Lee的其他文献
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{{ truncateString('Miler T. S. Lee', 18)}}的其他基金
Characterizing modes of maternal RNA degradation during vertebrate development
脊椎动物发育过程中母体 RNA 降解模式的表征
- 批准号:
8254551 - 财政年份:2012
- 资助金额:
$ 5.39万 - 项目类别:
Characterizing modes of maternal RNA degradation during vertebrate development
脊椎动物发育过程中母体 RNA 降解模式的表征
- 批准号:
8607201 - 财政年份:2012
- 资助金额:
$ 5.39万 - 项目类别:
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