Work

N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

Year: 2012
Type: review
Abstract: N(6)-methyl-adenosine (m(6)A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m(6)A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m(6)A may have a profound impact on gene expression regulation. The m(6)A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m(6)A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3'-untranslated region (3'-UTR) as revealed by high-throughput m(6)A-seq. One significant advance in m(6)A research is the recent discovery of the first two m(6)A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m(6)A demethylation in an α-ketoglutarate (α-KG)- and Fe(2+)-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m(6)A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m(6)A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.
Language: English
Open Access status: gold
Estimated APC paid: $3,850
OpenAlex ID: W1989683090
FWCI: 1.241
Cites: 109
Cited by: 524
Related to: 10