The RNA Modification N 6-Methyladenosine and Its Implications in Human Disease

Abstract

Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.

Topologies of N6‐adenosine methylation (m6A) in land plant mitochondria and their putative effects on organellar gene expression

“…m 6 A is not expected to rewire the genetic code for translation (Dai et al , ). m 6 A‐RNA modifications seem to serve important regulatory roles in gene expression in animals and plants, as well in various prokaryotic organism (see for example Batista, ; Meyer and Jaffrey, ; Arribas‐Hernández et al , ; Visvanathan and Somasundaram, ; and Yue et al , , and references therein).…”

Identification of three m6A‐related mRNAs signature and risk score for the prognostication of hepatocellular carcinoma

“…N6‐methyladenosine (m6A) is the most abundant internal modification of mRNA and long noncoding RNA in most eukaryotes . N6‐methyladenosine plays an important role in regulating mRNA splicing, translation, and stability .…”

The epitranscriptome in translation regulation: mRNA and tRNA modifications as the two sides of the same coin?

“…NSUN2 is a direct target gene of c-Myc, a well-known proto-oncogene and has been found to be upregulated in primary tumours and metastases of breast carcinomas [79]. The reduction in m 6 A levels through knockdown of Mettl3 results in tumour progression [77]. Taken together, these point to a crucial role of RNA modifications in human diseases.…”