Mobile small RNAs regulate genome-wide DNA methylation

MG Lewsey1, TJ Hardcastle2, CW Melnyk3, A Molnar4, A Valli2, MA Urich5, JR Nery5, DC Baulcombe2 and JR Ecker5,6,7

  1. Centre for AgriBioscience, Department of Animal, Plant and Soil Science, School of Life Science, La Trobe University, Bundoora, Australia
  2. Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK
  3. Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge CB2 1LR, UK
  4. School of Biological Sciences, The University of Edinburgh, Institute of Molecular Plant Sciences, Mayfield Road, Edinburgh EH9 3JR, UK
  5. Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
  6. Plant Biology Laboratory, The Salk Institute for Biological Studies
  7. Howard Hughes Medical Institute, The Salk Institute for Biological Studies

Small (s)RNAs of 21 to 24 nucleotides are associated with RNA silencing and methylation of DNA cytosine residues. All sizes can move from cell-to-cell and long distance in plants, directing RNA silencing in destination cells. Twenty-four nucleotide sRNAs are the predominant long-distance mobile species. Thousands move from shoot to root, where they target DNA methylation of transposable elements both directly and indirectly. We have identified several classes of interaction between sRNAs and DNA methylation and used these to examine the mechanisms of DNA methylation involved in long distance mobile sRNA signalling. We demonstrate that the pathways by which these mobile signals regulate DNA methylation are fundamentally distinct to those independent of a mobile signal. Direct and indirectly targeted mobile DNA methylation associate with the same superfamilies of transposable elements. They also depend upon the same RNA silencing mechanistic components. However, we show here that loci targeted directly can be distinguished from those targeted indirectly by the histone modifications with which they associate. Loci targeted directly associate with repressive histone modifications, whilst loci targeted indirectly associate with histone modifications found typically in active regions of the genome. This indicates functional differences exist between the classes of long distance mobile sRNA signals.