McCue Andrea D, Panda Kaushik, Nuthikattu Saivageethi, Choudury Sarah G, Thomas Erica N, Slotkin R Keith
Department of Molecular Genetics, The Ohio State University, Columbus, OH, USA.
Department of Molecular Genetics, The Ohio State University, Columbus, OH, USA
EMBO J. 2015 Jan 2;34(1):20-35. doi: 10.15252/embj.201489499. Epub 2014 Nov 11.
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.
转座元件（TEs）在活跃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（siRNAs）以及修饰TE染色质以表观遗传方式抑制转录的机制。由于参与TE转录后调控的小RNA群体与建立RNA指导的DNA甲基化（RdDM）的小RNA群体不同，转录活跃的TE从转录后RNA干扰调控转变为染色质水平控制的机制仍不清楚。我们已经确定了一种植物途径的分子机制，该途径可将DNA甲基化导向转录活跃的TE。我们证明，来自TE mRNA RNA干扰的21 - 22个核苷酸（nt）的siRNA降解产物直接整合到AGO6蛋白中，并将AGO6导向TE染色质，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，主要在配子发生之前将长着丝粒高拷贝转录活跃的TE靶向进行RdDM。这项研究提供了一种直接机制，弥合了TE转录后调控与TE表观遗传沉默建立之间的差距。
