RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
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DOI：
10.1101/gad.265215.115
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发表时间：
2015-07-01
影响因子：
10.5
通讯作者：
Hannon GJ
中科院分区：
文献类型：
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作者：
Wasik KA;Tam OH;Knott SR;Falciatori I;Hammell M;Vagin VV;Hannon GJ
在这项研究中，Wasik等人研究了PIWI相互作用Tudor蛋白的功能丧失如何影响减数分裂皮尔纳途径。他们的研究结果表明，在没有RNF 17的情况下，乒乓循环被去抑制，次级减数分裂皮尔纳的产生被抑制。RNF 17的缺失和乒乓循环的去阻遏也导致相当数量的基因的下调，这些基因在其UTR中含有转座子内容物，从而导致不育。总的来说，这项研究提供了新的见解乒乓球周期的调节和Rnf 17在男性生殖细胞发育过程中的作用。PIWI蛋白及其相关的piRNA保护生殖细胞免受移动的遗传元件的活性。两类piRNA-初级和次级-由它们的生物发生机制定义。初级piRNA直接从皮尔纳簇基因座的转录物加工，而次级piRNA在适应性扩增环（称为乒乓循环）中产生。在哺乳动物中，皮尔纳群体是动态的，随着雄性生殖细胞的发育而变化。胚胎piRNA由初级和次级种类组成，并且主要针对转座子。在减数分裂细胞中，皮尔纳群体是转座子贫乏的并且主要限于来源于粗线期皮尔纳簇的初级piRNA。从胚胎到成年皮尔纳途径的转变还没有很好地理解。在这里，我们表明RNF 17通过抑制次级piRNA的产生来塑造成体减数分裂皮尔纳含量。在没有RNF 17的情况下，乒乓运动在减数分裂细胞中不适当地发生。乒乓启动皮尔纳反应不仅针对转座子，而且针对蛋白质编码基因和长非编码RNA，包括生殖细胞发育所必需的基因。因此，Rnf 17突变体的不育可能是一种基于小RNA的自身免疫反应的表现。
In this study, Wasik et al. investigate how the loss of function of a PIWI-interacting Tudor protein affects the meiotic piRNA pathway. Their findings show that in the absence of RNF17, the ping-pong cycle is derepressed, and secondary meiotic piRNA production is suppressed. Loss of RNF17 and derepression of the ping-pong cycle also result in the down-regulation of considerable numbers of genes that harbor transposon content in their UTRs, resulting in sterility. Overall, this study provides novel insights into the regulation of the ping-pong cycle and the role of Rnf17 during male germ cell development. PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs—primary and secondary—are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction.