A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements.

A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements.
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DOI:
10.1155/2016/7595791
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发表时间:
2016
影响因子:
4.3
通讯作者:
Haase AD
Haase AD
中科院分区:
医学3区
文献类型:
--
作者:
Haase AD

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转座子是一种可移动的遗传元件,它通过破坏种系基因组的稳定来威胁物种的生存。限制这些自私因素的蔓延是当务之急。生殖细胞利用专门的小调控RNA途径来抑制转座子的活性。PIWI蛋白和PIWI相互作用rna (piRNAs)在转录和转录后水平沉默转座子,导致功能丧失的突变动物普遍表现出不育,通常与生殖细胞缺陷相关。这篇简短的综述旨在说明pirna引导的防御转座子的基本策略。piRNA沉默的机制在黑腹果蝇中最容易研究,它可以作为描述分子概念的模型,并作为哺乳动物piRNA系统的参考。PiRNA通路利用两种主要策略来应对转座子控制的挑战:(1)先前转座子的硬连接分子记忆能够识别移动遗传元件并区分转座子与宿主基因;(2)一种前馈适应机制塑造了piRNA群体,以选择性地对抗转座子转录本的直接威胁。在果蝇中,母体提供的PIWI-piRNA复合物加强了这两道防线,并确保了跨代免疫。虽然最近的研究已经提供了一个可以被视为古代免疫系统的概念框架,但我们才刚刚开始欣赏它的许多分子创新。
Transposons are mobile genetic elements that threaten the survival of species by destabilizing the germline genomes. Limiting the spread of these selfish elements is imperative. Germ cells employ specialized small regulatory RNA pathways to restrain transposon activity. PIWI proteins and Piwi-interacting RNAs (piRNAs) silence transposons at the transcriptional and posttranscriptional level with loss-of-function mutant animals universally exhibiting sterility often associated with germ cell defects. This short review aims to illustrate basic strategies of piRNA-guided defense against transposons. Mechanisms of piRNA silencing are most readily studied in Drosophila melanogaster, which serves as a model to delineate molecular concepts and as a reference for mammalian piRNA systems. PiRNA pathways utilize two major strategies to handle the challenges of transposon control: (1) the hard-wired molecular memory of prior transpositions enables recognition of mobile genetic elements and discriminates transposons from host genes; (2) a feed-forward adaptation mechanism shapes piRNA populations to selectively combat the immediate threat of transposon transcripts. In flies, maternally contributed PIWI-piRNA complexes bolster both of these lines of defense and ensure transgenerational immunity. While recent studies have provided a conceptual framework of what could be viewed as an ancient immune system, we are just beginning to appreciate its many molecular innovations.