DNA Methylation Mediated by a MicroRNA Pathway

Abstract

In plants, the known microRNAs (miRNAs) are produced as approximately 21 nucleotide (nt) duplexes from their precursors by Dicer-like 1 (DCL1). They are incorporated into Argonaute 1 (AGO1) protein to regulate target gene expression primarily through mRNA cleavage. We report here the discovery of a class of miRNAs in the model monocot rice (Oryza sativa). These are 24 nt in length and require another member of the Dicer family, DCL3, for their biogenesis. The 24 nt long miRNAs (lmiRNAs) are loaded into AGO4 clade proteins according to hierarchical rules, depending on the upstream biogenesis machinery and the 5'-terminal nucleotide. We demonstrated that lmiRNAs direct DNA methylation at loci from which they are produced as well as in trans at their target genes and play roles in gene regulation. Considered together, our findings define a miRNA pathway that mediates DNA methylation.

MicroRNAs in acute leukemia: from biological players to clinical contributors

“…80 Interestingly, a recent report demonstrated the discovery of a new class of miRNAs that directly (independent of target genes) mediated DNA methylation in plants. 81 After their loading into AGO4 clade proteins, these 24 nucleotide long miRNAs (lmiRNAs) directed DNA methylation at their own loci in cis as well as at their target genes in trans resulting a downregulation of target genes, likely via recruitment of de novo cytosine methyltransferase DRM2. 81 This fits in the hypothesis that Dicer processed miRNAs are required to maintain DNA methylation in human cancer cells.…”

“…81 After their loading into AGO4 clade proteins, these 24 nucleotide long miRNAs (lmiRNAs) directed DNA methylation at their own loci in cis as well as at their target genes in trans resulting a downregulation of target genes, likely via recruitment of de novo cytosine methyltransferase DRM2. 81 This fits in the hypothesis that Dicer processed miRNAs are required to maintain DNA methylation in human cancer cells. 82 In summary, miRNAs may function both as bystander and as actor of the epigenetic control of gene expression.…”

Genome-Wide Characterization of Maize Small RNA Loci and Their Regulation in the required to maintain repression6-1 (rmr6-1) Mutant and Long-Term Abiotic Stresses

“…After the duplex is loaded into ARGONAUTE 1, the miRNA guide strand is most frequently retained and directs target repression, while the miRNA* is more often rapidly degraded. Most plant miRNAs induce post-TGS of their targets, but some cases of TGS have been described (Bao et al, 2004;Wu et al, 2010;Hu et al, 2014). Plant miRNAs share extensive sequence complementarity with their target RNAs: there are only a few examples with more than five mismatches between the miRNA and the target (Axtell, 2013a).…”

The use of high-throughput sequencing methods for plant microRNA research

“…According to the previous study, the 5 0 U-started, 21-nt miRNAs are preferentially recruited by the AGO1 protein complex in Arabidopsis. 5 However, our statistical result shows that a significant portion of the plant miRNAs registered in miRBase ( release 21) 28 discovered a new miRNA species of 24 nt in rice. These miRNAs were called long miRNAs (lmiRNAs).…”

“…Different from the canonical miRNAs, the biogenesis of the lmiRNAs depends on DCL3, and they are incorporated into the AGO4 clade proteins to mediate site-specific DNA methylation. 28 More complicatedly, in Arabidopsis, there are 10 AGO proteins, several studies demonstrate that different AGO genes have their specific spatio-temporal expression patterns. [29][30][31][32] Taken together, by using sRNA-seq data prepared from different AGO proteins, the spatio-temporal AGO loading patterns of the miRNAs along with their sequence features could be deeply investigated.…”