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

By Y. Niu, Xu Zhao, Yong-Sheng Wu, Ming-Ming Li, Xiu-Jie Wang, Yun-Gui Yang. Genomics, Proteomics & Bioinformatics, 2012

445 citations recorded by the source corpus.

N6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3′-untranslated region (3′-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-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 m6A 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 m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.

Subfields: Cancer Research, Energy Engineering and Power Technology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9ed4641dde76999144352a7682c0f5defe5d974f

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Citations in the corpus

Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5 (2014, background): “These studies have provided new insights into the distribution and functional role of m6A in mRNA (10,11).”
m6A RNA modification controls cell fate transition in mammalian embryonic stem cells (2014, background): “While m6A has been suggested to affect almost all aspects of RNA metabolism, the molecular function of this modification remains incompletely understood (Niu et al., 2013).”
METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6‐methyladenosine‐dependent primary MicroRNA processing (2017, background): “Further studies might be required in the following aspects: (1) to quantify the m(6)A levels of HCC more accurately using mass spectrometry or thin layer chromatography, (2) to identify the target genes of METTL14 through high-throughput analysis, (3) to elucidate the reason for the METTL14 decrease”