Just like the Beatles, evolution appears to work best in harmony with all its members. RNA-mediated inheritance, a key component of the epigenetic mix, has quickly risen into the spotlight of mechanisms for non-Mendelian heredity.
Dr. Minoo Rassoulzadegan’s group (University of Nice Sophia Antipolis, France) has previously shown that small non-coding RNAs can cause heritable epigenetic alterations in mice, which act as “trans-generational signaling molecules”. In their latest research they examined the nitty gritties behind two model paramutations. Paramutations are an epigenetic phenomenon involving the interaction between two alleles at a single locus, where the allele from one parent induces a heritable epigenetic change (such as DNA methylation) in the allele from the other parent. In this case they looked at Kit, where paramutation causes discoloration of the tail and feet, and Sox9, where paramutation causes an overgrowth phenotype.
Given the previous implication of small non-coding RNAs in these paramutations, they decided to further examine the players in this transgenerational process. They decided to examine Dmnt2, because while it looks and smells like a DNA methyltransferase, it’s a protein of controversial nature and has actually only been shown to catalyze cytosine methylation in some RNA substrates (and not DNA).
Here’s what they found:
- The Kit and Sox9 paramutant phenotypes were not transmitted to the progeny of Dnmt2 knockout mice.
- No changes were seen in the DNA methylation status of the Kit locus between the wild-type and paramutant mice.
- RNA bisulfite sequencing indicated Dnmt2-dependent cytosine methylation in Kit RNA in paramutant embryos.
This research demonstrates that the role of the “enigmatic” Dmnt2 as a RNA methyltransferase is necessary for the establishment and transgenerational signaling of both paramutations. Ultimately, in this case, it appears that RNA methylation by Dmnt2 is involved in epigenetic heredity, although it gets by with a little help from its DNA methylation machinery friends.
Read more in PLOS Genetics, May 2013