ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation

作者：McCue Andrea D; Panda Kaushik; Nuthikattu Saivageethi; Choudury Sarah G; Thomas Erica N; Slotkin R Keith^*

来源：The EMBO Journal, 2015, 34(1): 20-35.

DOI：10.15252/embj.201489499

• Argonaute
• epigenetics
• RNA-directed DNA methylation
• small interfering RNA
• transposable element

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.

• 出版日期2015-1-2