ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation
ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation
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DOI：
10.15252/embj.201489499
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发表时间：
2015-01-02
期刊：
影响因子：
11.4
通讯作者：
Slotkin, R. Keith
中科院分区：
文献类型：
--
作者：
McCue, Andrea D.;Panda, Kaushik;Slotkin, R. Keith
转座因子（te）在激活时会产生突变和染色体不稳定。为了抑制TE活性，真核细胞进化出了将TE mrna降解为小干扰rna （sirna）和修饰TE染色质以表观遗传抑制转录的机制。由于参与TE转录后调控的小rna群体与建立rna定向DNA甲基化（RdDM）的小rna群体不同，因此转录活性TE从转录后RNAi调控转变为染色质水平控制的机制尚不清楚。我们已经确定了植物途径的分子机制，该途径的功能是将DNA甲基化引导到转录活性te。我们证明了TE mrna的RNAi的21-22个核苷酸（nt） siRNA降解产物被直接结合到ARGONAUTE 6 （AGO6）蛋白中，并将AGO6引导到TE染色质上，以指导其在RdDM中的功能。我们发现该途径在生殖前体细胞中起作用，主要针对配子体发生前的RdDM的长着丝粒高拷贝转录活性te。本研究为TE转录后调控与TE表观遗传沉默的建立之间的联系提供了一个直接的机制。
Transposable elements (TEs) generate mutations and chromosomal instability when active. To repress TE activity, eukaryotic cells evolved mechanisms to both degrade TE mRNAs into small interfering RNAs (siRNAs) and modify TE chromatin to epigenetically inhibit transcription. Since the populations of small RNAs that participate in TE post-transcriptional regulation differ from those that establish RNA-directed DNA methylation (RdDM), the mechanism through which transcriptionally active TEs transition from post-transcriptional RNAi regulation to chromatin level control has remained unclear. We have identified the molecular mechanism of a plant pathway that functions to direct DNA methylation to transcriptionally active TEs. We demonstrated that 21-22 nucleotide (nt) siRNA degradation products from the RNAi of TE mRNAs are directly incorporated into the ARGONAUTE 6 (AGO6) protein and direct AGO6 to TE chromatin to guide its function in RdDM. We find that this pathway functions in reproductive precursor cells to primarily target long centromeric high-copy transcriptionally active TEs for RdDM prior to gametogenesis. This study provides a direct mechanism that bridges the gap between the post-transcriptional regulation of TEs and the establishment of TE epigenetic silencing.