FIGURE 1. MicroRNA-mediated methylation of genomic DNA.

Bao et al.⁴ find that methylation (the addition of CH₃ groups) occurs in the PHB and PHV genes; they suggest that this must involve microRNAs (miRNAs), as mutations that disrupt the genes' miRNA-binding sites prevent methylation. How might methylation occur? In the proposed models, mature miRNA is first produced from a precursor and exported from the nucleus. a, The mature miRNA might return to the nucleus with an RNA-induced silencing complex (RISC), and base-pair to a matching sequence (red) in the messenger RNA (mRNA) being produced from PHB/PHV. The RISC might then, via the mRNA, recruit 'chromatin-remodelling' machinery to the DNA to achieve methylation. b, Small interfering RNAs (siRNAs) might be produced by an RNA-dependent RNA polymerase, directed by miRNAs or by miRNA-induced mRNA cleavage. The siRNAs might then directly or indirectly (via 'spreading') target the gene's blue region for methylation. c, The mRNA could be modified by an miRNA-induced 'mark' (such as cleavage), and then guided to the DNA to induce methylation.