Maternal and zygotic gene regulatory effects of endogenous RNAi pathways
Maternal and zygotic gene regulatory effects of endogenous RNAi pathways
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DOI：
10.1371/journal.pgen.1007784
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发表时间：
2019-02-01
期刊：
影响因子：
4.5
通讯作者：
Ketting, Rene F.
中科院分区：
文献类型：
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作者：
Almeida, Miguel Vasconcelos;Domingues, Antonio Miguel de Jesus;Ketting, Rene F.
内源性小RNA（sRNA）和Argonaute蛋白是生殖系和体细胞组织中普遍存在的基因表达调节因子。sRNA-Argonaute复合物通常在配子中表达，因此在受精后由下一代遗传。在秀丽隐杆线虫中，26 G-RNA是触发下游次级sRNA表达的主要内源sRNA。存在两个26 G-RNA亚群，每个亚群都显示出强烈的区室化表达：一个在生精性腺中表达，与Argonaute ALG-3/4相关;另一个在卵母细胞和胚胎中表达，与Argonaute ERGO-1相关。由26 G-RNA引起的基因沉默的决定因素和动力学在很大程度上是未知的。在这里，我们提供了各种新的见解，这些内源性sRNA途径的C。优雅的。利用遗传学和深度测序，我们剖析了26 G-RNA通路的ERGO-1分支的母体效应。我们发现，即使在没有合子初级触发物的情况下，母体初级sRNA也可以触发合子次级sRNA的产生，所述合子次级sRNA能够使靶沉默。因此，母体和合子sRNA群体的相互作用确保了整个动物发育过程中靶基因的沉默。此外，我们还探索了与ALG-3/4分支相关的26 G-RNA生物学的其他方面。我们发现sRNA丰度、sRNA来源模式和靶转录物的3' UTR长度是Argonautes ALG-3/4调控结果的预测因子。最后，我们提供的证据表明ALG-3和ALG-4以负反馈循环调节其自身的mRNA。总之，我们提供了一些新的监管见解的动力学，目标调控和自我调节的内源性RNAi途径的C。小RNA（sRNA）和它们的伴侣Argonaute蛋白调节靶RNA的表达。当精子和卵子在受精时相遇时，一组不同的蛋白质和RNA，包括sRNA-Argonaute复合物，被传递给发育中的后代。因此，这两个参与者对于启动下一代的特定基因表达程序非常重要。线虫秀丽隐杆线虫表达几类sRNA。26 G-RNA是一类特殊的sRNA，分为两个亚群：一个在生精性腺中表达，另一个在卵母细胞和胚胎中表达。在这项工作中，我们描述了动态，从而卵子26 G-RNA设置基因沉默在下一代。此外，我们还展示了生精26 G-RNA及其伴侣Argonaute，ALG-3和ALG-4用于调节其靶点的几种方式。最后，我们发现ALG-3和ALG-4正在微调自己的表达，这是Argonaute蛋白的一种罕见作用。总的来说，我们为sRNA和Argonaute如何调节基因表达提供了新的见解。
Endogenous small RNAs (sRNAs) and Argonaute proteins are ubiquitous regulators of gene expression in germline and somatic tissues. sRNA-Argonaute complexes are often expressed in gametes and are consequently inherited by the next generation upon fertilization. In Caenorhabditis elegans, 26G-RNAs are primary endogenous sRNAs that trigger the expression of downstream secondary sRNAs. Two subpopulations of 26G-RNAs exist, each of which displaying strongly compartmentalized expression: one is expressed in the spermatogenic gonad and associates with the Argonautes ALG-3/4; plus another expressed in oocytes and in embryos, which associates with the Argonaute ERGO-1. The determinants and dynamics of gene silencing elicited by 26G-RNAs are largely unknown. Here, we provide diverse new insights into these endogenous sRNA pathways of C. elegans. Using genetics and deep sequencing, we dissect a maternal effect of the ERGO-1 branch of the 26G-RNA pathway. We find that maternal primary sRNAs can trigger the production of zygotic secondary sRNAs that are able to silence targets, even in the absence of zygotic primary triggers. Thus, the interaction of maternal and zygotic sRNA populations, assures target gene silencing throughout animal development. Furthermore, we explore other facets of 26G-RNA biology related to the ALG-3/4 branch. We find that sRNA abundance, sRNA pattern of origin and the 3' UTR length of target transcripts are predictors of the regulatory outcome by the Argonautes ALG-3/4. Lastly, we provide evidence suggesting that ALG-3 and ALG-4 regulate their own mRNAs in a negative feedback loop. Altogether, we provide several new regulatory insights on the dynamics, target regulation and self-regulation of the endogenous RNAi pathways of C. elegans.Author summary Small RNAs (sRNAs) and their partner Argonaute proteins regulate the expression of target RNAs. When sperm and egg meet upon fertilization, a diverse set of proteins and RNA, including sRNA-Argonaute complexes, is passed on to the developing progeny. Thus, these two players are important to initiate specific gene expression programs in the next generation. The nematode Caenorhabditis elegans expresses several classes of sRNAs. 26G-RNAs are a particular class of sRNAs that are divided into two subpopulations: one expressed in the spermatogenic gonad and another expressed in oocytes and in embryos. In this work, we describe the dynamics whereby oogenic 26G-RNAs setup gene silencing in the next generation. In addition, we show several ways that spermatogenic 26G-RNAs and their partner Argonautes, ALG-3 and ALG-4, use to regulate their targets. Finally, we show that ALG-3 and ALG-4 are fine-tuning their own expression, a rare role of Argonaute proteins. Overall, we provide new insights into how sRNAs and Argonautes are regulating gene expression.