piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting.
piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting.
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DOI：
10.1093/nar/gkab1290
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发表时间：
2022-02-22
影响因子：
14.9
通讯作者：
Wingreen NS
中科院分区：
文献类型：
--
作者：
McEnany J;Meir Y;Wingreen NS
piRNA 等小非编码 RNA 是 Argonaute 蛋白的向导，能够实现基因表达的序列特异性、转录后调控。与果蝇和其他生物体中的 piRNA 不同，秀丽隐杆线虫的 piRNA 与具有高错配耐受性的靶标结合，并且似乎缺乏特定的转座子靶标。这些观察结果支持了一个模型，其中线虫 piRNA 提供了广泛的、不加区别的沉默网络，与专门保护自身基因免遭沉默的 CSR-1 Argonaute 相关的 siRNA 竞争。然而，piRNA 靶向的广度尚未得到深入的定量分析，也没有解释 piRNA 如何分布在序列空间以实现完全覆盖。通过对 piRNA 序列的生物信息学分析，结合基于原始数据的 piRNA-目标距离度量，我们证明了线虫 piRNA 在功能上是随机的，因为它们的序列空间覆盖范围与随机序列的覆盖范围相当。通过拥有足够数量的不同的、本质上随机的 piRNA，线虫能够以高概率靶向任意非自身序列。我们将这种方法扩展到其他线虫，发现了阐明非自身 mRNA 沉默机制的结果，并对 piRNA 进化和生物发生具有影响。
Small noncoding RNAs such as piRNAs are guides for Argonaute proteins, enabling sequence-specific, post-transcriptional regulation of gene expression. The piRNAs of Caenorhabditis elegans have been observed to bind targets with high mismatch tolerance and appear to lack specific transposon targets, unlike piRNAs in Drosophila melanogaster and other organisms. These observations support a model in which C. elegans piRNAs provide a broad, indiscriminate net of silencing, competing with siRNAs associated with the CSR-1 Argonaute that specifically protect self-genes from silencing. However, the breadth of piRNA targeting has not been subject to in-depth quantitative analysis, nor has it been explained how piRNAs are distributed across sequence space to achieve complete coverage. Through a bioinformatic analysis of piRNA sequences, incorporating an original data-based metric of piRNA-target distance, we demonstrate that C. elegans piRNAs are functionally random, in that their coverage of sequence space is comparable to that of random sequences. By possessing a sufficient number of distinct, essentially random piRNAs, C. elegans is able to target arbitrary nonself sequences with high probability. We extend this approach to a selection of other nematodes, finding results which elucidate the mechanism by which nonself mRNAs are silenced, and have implications for piRNA evolution and biogenesis.
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影响因子：
14.9
作者：
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通讯作者：
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通讯作者：
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