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A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases
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A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases
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A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases
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Journal Article
A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases
2008
Overview
Dicer initiates RNA interference by generating small RNAs involved in various silencing pathways. Dicer participates in centromeric silencing, but its role in the epigenetic regulation of other chromatin domains has not been explored. Here we show that
Dicer1
deficiency in
Mus musculus
leads to decreased DNA methylation, concomitant with increased telomere recombination and telomere elongation. These DNA-methylation defects correlate with decreased expression of Dnmt1, Dnmt3a and Dnmt3b DNA methyltransferases (Dnmts), and methylation levels can be recovered by their overexpression. We identify the retinoblastoma-like 2 protein (Rbl2) as responsible for decreased Dnmt expression in
Dicer1
-null cells, suggesting the existence of Dicer-dependent small RNAs that target Rbl2. We identify the miR-290 cluster as being downregulated in
Dicer1
-deficient cells and show that it silences
Rbl2
, thereby controlling Dnmt expression. These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Chromosomal Proteins, Non-Histone - metabolism
/ DEAD-box RNA Helicases - metabolism
/ DNA
/ DNA (Cytosine-5-)-Methyltransferase 1
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ Endoribonucleases - metabolism
/ Mice
/ Retinoblastoma-Like Protein p130 - metabolism
/ RNA
