An siRNA-guided ARGONAUTE protein directs RNA polymerase V to initiate DNA methylation

• Published in: Nature plants Vol. 7; no. 11; pp. 1461 - 1474
• Main Authors: Sigman, Meredith J, Panda, Kaushik, Kirchner, Rachel, McLain, Lauren L, Payne, Hayden, Peasari, John Reddy, Husbands, Aman Y, Slotkin, R Keith, McCue, Andrea D
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2021; Nature Publishing Group UK
• Subjects: Arabidopsis; Argonaute Proteins - genetics; Cytosine; Deoxyribonucleic acid; DNA; DNA Methylation; DNA Transposable Elements - genetics; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Epigenetics; Loci; Proteins; Recruitment; Ribonucleic acid; RNA; RNA polymerase; RNA, Small Interfering - genetics; siRNA
• ISSN: 2055-0278; 2055-0278
• DOI: 10.1038/s41477-021-01008-7

In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without pre-existing DNA methylation. We find that Pol V follows and is dependent on the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of pre-existing DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.