通过piRNA调节索马和生殖系中的转子子替代拼接
Felipe Karam Teixeira1, Martyna Okuniewska1, Colin D Malone1
1Howard Hughes Medical Institute (HHMI) and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Nature
|December 7, 2017
概括
皮维相互作用RNA (piRNA) 途径通过控制前体mRNA拼接来调节可移植元素,而不仅仅是转录水平. 这种机制可以保护Drosophila的基因组免受转体子的移动.
科学领域:
- 遗传学
- 分子生物学
- 表观遗传学
背景情况:
- 可移植元素 (TE) 是可驱动基因组进化的移动基因序列,但需要严格监管以防止宿主受损.
- 皮维相互作用RNA (piRNA) 途径对于TE控制至关重要,主要通过转录沉默或mRNA衰变.
- P元素和吉普赛逆转移体是Drosophila中关键的TEs,它们的活性会影响生殖线的发育和基因组的稳定性.
研究的目的:
- 调查piRNA途径在规范可转移元素活动之外的作用.
- 阐明piRNA途径组件在体内和体外影响P元素和吉普赛逆转录素的特定机制.
- 在基因组防御中确定piRNA路径的新功能及其与染色体结构和替代拼接的相互作用.
主要方法:
- 在Drosophila生殖细胞中进行体内研究,以分析P元素转录组合.
- 研究piRNA通路组件,包括Asterix (Gtsf1),Panoramix (Silencio) 和异染色蛋白1a (HP1a),用于调节TE拼接.
- 在培养的卵巢体细胞中分析吉普赛逆转移素与Flamenco piRNA集群的结合.
主要成果:
- 该piRNA途径调节P转移元素转录的前体mRNA拼接,产生非转移酶mRNA异型.
- 与预期相反,piRNA路径组件在P- M混合失调过程中不会降低P元素转录水平.
- 剪接调节与抑制色素状态的piRNA介导的变化有关,包括Asterix,Panoramix和HP1a等关键蛋白质.
- 该piRNA路径和Flamenco集群也控制吉普赛逆转录素的积累,并调节体细胞中的吉普赛mRNA拼接.
结论:
- 拼接调节是Piwi通路在保护基因组免受转体子移动性方面的新和重要功能.
- 这项研究揭示了一种协调的机制,涉及piRNA介导的染色质修饰和替代拼接来控制TE活性.
- 这为了解染色体结构如何影响发育过程中的替代拼接和TE调节提供了有价值的模型.
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