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E7.5小鼠原生殖层的全转录组剪接分析揭示了小鼠早期胚胎发育过程中频繁使用可变启动子的现象。

Whole-transcriptome splicing profiling of E7.5 mouse primary germ layers reveals frequent alternative promoter usage during mouse early embryogenesis.

作者信息

Lu Xukun, Zhao Zhen-Ao, Wang Xiaoqing, Zhang Xiaoxin, Zhai Yanhua, Deng Wenbo, Yi Zhaohong, Li Lei

机构信息

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Biol Open. 2018 Mar 28;7(3):bio032508. doi: 10.1242/bio.032508.

Abstract

Alternative splicing (AS) and alternative promoter (AP) usage expand the repertories of mammalian transcriptome profiles and thus diversify gene functions. However, our knowledge about the extent and functions of AS and AP usage in mouse early embryogenesis remains elusive. Here, by performing whole-transcriptome splicing profiling with high-throughput next generation sequencing, we report that AS extensively occurs in embryonic day (E) 7.5 mouse primary germ layers, and may be involved in multiple developmental processes. In addition, numerous RNA splicing factors are differentially expressed and alternatively spliced across the three germ layers, implying the potential importance of AS machinery in shaping early embryogenesis. Notably, AP usage is remarkably frequent at this stage, accounting for more than one quarter (430/1,648) of the total significantly different AS events. Genes generating the 430 AP events participate in numerous biological processes, and include important regulators essential for mouse early embryogenesis, suggesting that AP usage is widely used and might be relevant to mouse germ layer specification. Our data underline the potential significance of AP usage in mouse gastrulation, providing a rich data source and opening another dimension for understanding the regulatory mechanisms of mammalian early development.

摘要

可变剪接(AS)和可变启动子(AP)的使用扩展了哺乳动物转录组图谱的种类,从而使基因功能多样化。然而,我们对小鼠早期胚胎发育过程中AS和AP使用的程度及功能仍知之甚少。在此,通过利用高通量下一代测序技术进行全转录组剪接分析,我们报告称AS广泛存在于胚胎第7.5天(E7.5)的小鼠原肠胚层中,并可能参与多个发育过程。此外,众多RNA剪接因子在三个胚层中差异表达且发生可变剪接,这意味着AS机制在塑造早期胚胎发育过程中具有潜在重要性。值得注意的是,在此阶段AP的使用非常频繁,占所有显著不同AS事件总数的四分之一以上(430/1648)。产生这430个AP事件的基因参与众多生物学过程,包括对小鼠早期胚胎发育至关重要的重要调节因子,这表明AP的使用被广泛采用,并且可能与小鼠胚层特化相关。我们的数据强调了AP使用在小鼠原肠胚形成中的潜在重要性,提供了丰富的数据源,并为理解哺乳动物早期发育的调控机制开辟了新的维度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e680/5898269/c0f78f791ff6/biolopen-7-032508-g1.jpg

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