RNA Methylation and Metabolism

Abstract

Molecular Biology The methylation—and demethylation—of DNA play an important role in the dynamic regulation of gene expression and in genome stability. RNA in eukaryotes is also methylated on the A base (m6A), the most abundant posttranscriptional modification of mammalian mRNA. The modification is known to have biological function in meiosis and sporulation in yeast and potentially in RNA processing in mammalian cells. Zheng et al. identify a mammalian RNA demethylase, ALKBH5, that is capable of removing the m6A mark from RNA both in vitro and in vivo. The ALKBH5 protein localized to nuclear speckles and associated with specific mRNA processing factors there, and also affected mRNA export, with both functions requiring the ALKBH5 demethylation activity. A knockout of the ALKBH5 gene in mice resulted in reduced male fertility and revealed that the demethylase influences the expression of many genes, including key genes involved in spermatogenesis, resulting in defects in spermatogenesis and aberrant apoptosis in the testes of the mutant male mice. Thus, the dynamic methylation and demethylation of RNA, like DNA, may play an important role in gene regulation. Mol. Cell 49 , 18 (2013).