Methylation is a hot topic in the field of epigenetics whether it’s occurring on the cytosines of DNA or its histone protein friends. With a relatively well-known set of enzymes, methylation marks are dynamically modified in order to regulate gene expression.
However, the revisiting of a RNA modification discovered in the 70’s has come to show that post-translational modifications to RNA have the potential to influence the epigenetic landscape just as well.
Methylation of N6-methyladenine (m6A) is the most prevalent internal modification on mRNA and long non-coding RNA. Recently, Dr. Cuan He’s team at the University of Chicago (Go Bulls) have made some groundbreaking discoveries. Here are the highlights of their recent findings:
- The AlkB family of dioxygenases, specifically Alkbh5 and FTO, are capable of oxidatively reversing the methylation of m6A and serve as novel RNA demethylases.
- These enzymes participate in a variety of biological pathways and are widely expressed across multiple tissues.
- Alkbh5 is most highly expressed in the testis and a knockout in mice resulted in impaired male fertility due to compromised spermatogenesis.
- They also observed increased m6A levels in mRNA isolated from the knockout mouse organs.
- Interestingly, their RNA-Seq results indicated altered gene expression in the cells of testes from their knockout mice, thus showing that the loss of the m6A demethylase influences gene expression and results in compromised spermatogenesis.
Given the genome wide observance of m6a by other groups, these finding challenge our conventional perceptions of where epigenetic marks occur. Ultimately, it appears that RNA modifications are not only reversible, but given their dynamic nature they have important regulatory functions that are yet to be fully appreciated.
Read all about it in RNA Biology, April 2013