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RNA structural dynamics regulate early embryogenesis through controlling transcriptome fate and function

机译:RNA结构动力学通过控制转录组命运和功能调节早期胚胎发生

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BACKGROUND:Vertebrate early embryogenesis is initially directed by a set of maternal RNAs and proteins, yet the mechanisms controlling this program remain largely unknown. Recent transcriptome-wide studies on RNA structure have revealed its pervasive and crucial roles in RNA processing and functions, but whether and how RNA structure regulates the fate of the maternal transcriptome have yet to be determined.RESULTS:Here we establish the global map of four nucleotide-based mRNA structures by icSHAPE during zebrafish early embryogenesis. Strikingly, we observe that RNA structurally variable regions are enriched in the 3' UTR and contain cis-regulatory elements important for maternal-to-zygotic transition (MZT). We find that the RNA-binding protein Elavl1a stabilizes maternal mRNAs by binding to the cis-elements. Conversely, RNA structure formation suppresses Elavl1a's binding leading to the decay of its maternal targets.CONCLUSIONS:Our study finds that RNA structurally variable regions are enriched in mRNA 3' UTRs and contain cis-regulatory elements during zebrafish early embryogenesis. We reveal that Elavl1a regulates maternal RNA stability in an RNA structure-dependent fashion. Overall, our findings reveal a broad and fundamental role of RNA structure-based regulation in vertebrate early embryogenesis.
机译:背景:脊椎动物早期胚胎发生最初由一组母体RNA和蛋白质引导,然而控制该程序的机制仍然很大程度上是未知的。最近关于RNA结构的转录组研究已经揭示了RNA加工和功能的普遍性和至关重要的作用,但RNA结构是否以及如何调节母体转录组的命运尚未确定。结果:在这里,我们建立了四个全球地图斑马鱼早期胚胎发生过程中ICSHAPE基于核苷酸的mRNA结构。令人惊讶的是,我们观察到RNA结构可变区富集在3'UTR中,并含有对母体至血基转变(MZT)重要的顺式调节元件。我们发现RNA结合蛋白ELAV11a通过与顺式元素结合而稳定母体MRNA。相反,RNA结构形成抑制ELAVL1A的结合导致其母体靶标的衰减。结论:我们的研究发现,在斑马鱼早期胚胎发生过程中富含RNA结构可变区并含有顺式调节元件。我们揭示了ELAVL1A以RNA结构依赖的方式调节母体RNA稳定性。总体而言,我们的研究结果揭示了基于RNA结构的调节在脊椎动物早期胚胎发生中的一种广泛而基本的作用。

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