26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans

26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans
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DOI:
10.1073/pnas.0906378106
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发表时间:
2009-11-03
影响因子:
11.1
通讯作者:
Kim, John K.
Kim, John K.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Han, Ting;Manoharan, Arun Prasad;Kim, John K.

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内源性小干扰RNA(endo-siRNA)通过结合和切割mRNA靶标或介导异染色质形成来调节真核生物中的多种基因表达程序;然而,endo-siRNA生物合成、分选和靶标调节的机制仍然知之甚少。在这里,我们报告了秀丽隐杆线虫中一类特定的种系产生的endo-siRNA的鉴定和功能,这些endo-siRNA长26 nt,在第一个核苷酸位置含有鸟嘌呤(即,26G RNA)。26 G RNA在精子发生和合子发育过程中调节基因表达,它们的生物发生需要ERI-1外切核酸酶和RRF-3 RNA依赖性RNA聚合酶(RdRP)。值得注意的是,我们确定了26 G RNA的两个不重叠的亚类,它们分为特定的RNA诱导沉默复合物(RISC),并差异调节不同的mRNA靶点。I类26 G RNA靶基因在精子发生过程中表达,而II类26 G RNA是母系遗传的,在合子发育过程中沉默基因表达。这些发现暗示了一类endo-siRNA在生育和发育所需的转录程序的全局调节中。
Endogenous small interfering RNAs (endo-siRNAs) regulate diverse gene expression programs in eukaryotes by either binding and cleaving mRNA targets or mediating heterochromatin formation; however, the mechanisms of endo-siRNA biogenesis, sorting, and target regulation remain poorly understood. Here we report the identification and function of a specific class of germline-generated endo-siRNAs in Caenorhabditis elegans that are 26 nt in length and contain a guanine at the first nucleotide position (i.e., 26G RNAs). 26G RNAs regulate gene expression during spermatogenesis and zygotic development, and their biogenesis requires the ERI-1 exonuclease and the RRF-3 RNA-dependent RNA polymerase (RdRP). Remarkably, we identified two nonoverlapping subclasses of 26G RNAs that sort into specific RNA-induced silencing complexes (RISCs) and differentially regulate distinct mRNA targets. Class I 26G RNAs target genes are expressed during spermatogenesis, whereas class II 26G RNAs are maternally inherited and silence gene expression during zygotic development. These findings implicate a class of endo-siRNAs in the global regulation of transcriptional programs required for fertility and development.