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Co-activation of microRNAs by Zelda is essential for early drosophila development

机译:Zelda对microRNA的共激活对于果蝇的早期发育至关重要

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Transcription factors and microRNAs (miRNAs) are two important classes of trans-regulators in differential gene expression. Transcription factors occupy cis-regulatory motifs in DNA to activate or repress gene transcription, whereas miRNAs specifically pair with seed sites in target mRNAs to trigger mRNA decay or inhibit translation. Dynamic spatiotemporal expression patterns of transcription factors and miRNAs during development point to their stage- and tissue- specific functions. Recent studies have focused on miRNA functions during development; however, much remains to explore regarding how the expression of miRNAs is initiated and how dynamic miRNA expression patterns are achieved by transcriptional regulatory networks at different developmental stages. Here, we focused on the identification, regulation and function of miRNAs during the earliest stage of Drosophila development, when the maternal-to- zygotic transition (MZT) takes place. Eleven miRNA clusters comprise the first set of miRNAs activated in the blastoderm embryo. The transcriptional activator Zelda is required for their proper activation and regulation, and Zelda binding observed in genome-wide binding profiles is predictive of enhancer activity. In addition, other blastoderm transcription factors, comprising both activators and repressors, the activities of which are potentiated and coordinated by Zelda, contribute to the accurate temporal and spatial expression of these miRNAs, which are known to function in diverse developmental processes. Although previous genetic studies showed no early phenotypes upon loss of individual miRNAs, our analysis of the miR-1; miR-9a double mutant revealed defects in gastrulation, demonstrating the importance of co-activation of miRNAs by Zelda during the MZT.
机译:转录因子和microRNA(miRNA)是差异基因表达中的两类重要的反式调节因子。转录因子占据DNA中的顺式调控基序,以激活或抑制基因转录,而miRNA与目标mRNA中的种子位点特异性配对,从而触发mRNA降解或抑制翻译。转录因子和miRNA在发育过程中的动态时空表达模式指向其阶段和组织特异性功能。最近的研究集中在发育过程中的miRNA功能上。但是,关于如何启动miRNA的表达以及如何通过不同发育阶段的转录调控网络实现动态miRNA表达模式的研究还有很多。在这里,我们着重于果蝇发育的最初阶段,即母体-合子转变(MZT)发生时,miRNA的鉴定,调控和功能。 11个miRNA簇包含在胚盘胚中激活的第一组miRNA。转录激活因子Zelda是其正确激活和调节所必需的,而在全基因组结合谱中观察到的Zelda结合可预测增强子的活性。此外,包含激活子和阻遏物的其他胚盘转录因子,其活性受Zelda增强和协调,有助于这些miRNA的精确时空表达,已知这些miRNA在多种发育过程中发挥作用。尽管先前的遗传研究显示丢失单个miRNA后没有早期表型,但我们对miR-1的分析; miR-9a双重突变体揭示了胃排毒中的缺陷,表明在MZT期间Zelda对miRNA进行共激活的重要性。

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