John-Arne Dahl (photo), from Arne Klungland's group at the Department of Microbiology, Oslo University Hospital, shares the first-autorship on a collaborative work entitled "ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility", published in the prestigious journal "Molecular Cell" (impact factor 14.178).
This article is now available in print and it was selected as "Editor's choice" in the February 1st issue of the influential magazine Science.
Methylation of mammalian DNA and histone residues are known to regulate transcription, and the discovery of demethylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. Knowledge on these demethylases has led to a tremendous progress in the understanding of methyl marks in gene regulation and role in numerous diseases.
In mRNA, the methylation of adenosine (6meA) is particularly interesting since it is the most abundant internal modification. The first mRNA demethylase, FTO, was identified recently and 6meA was shown to be a substrate for FTO. Genome-wide association studies have identified a firm link between the human FTO gene, obesity and type II diabetes.
In a collaborative study, John Arne Dahl and colleagues, together with collaborators at the University of Chicago and Beijing, show that ALKBH5 is a second demethylase for 6meA in mRNA (see figure below) and that mice lacking this demethylase are infertile. Peter Fedorcsak from the Department of Gynecology, Oslo University Hospital, has also contributed for characterizing infertility in Alkbh5 defective mice.
Together, the discovery of two proteins that can reverse 6meA modifications from mRNA draws attention to the potential regulatory functions of reversible RNA methylation and the role of 6meA in disease. Insights into the mechanism of this process may well open up new horizons and opportunities for basic as well as translational research.
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility.
Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vågbø CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C.
Mol Cell. 2013 Jan 10;49(1):18-29. doi: 10.1016/j.molcel.2012.10.015. Epub 2012 Nov 21.