Interplay Between N 6-Methyladenosine (m6A) and Non-coding RNAs in Cell Development and Cancer - PubMed (original) (raw)

Review

Interplay Between N 6-Methyladenosine (m6A) and Non-coding RNAs in Cell Development and Cancer

Francesco Fazi et al. Front Cell Dev Biol. 2019.

Abstract

RNA chemical modifications in coding and non-coding RNAs have been known for decades. They are generally installed by specific enzymes and, in some cases, can be read and erased by other specific proteins. The impact of RNA chemical modifications on gene expression regulation and the reversible nature of some of these modifications led to the birth of the word epitranscriptomics, in analogy with the changes that occur on DNA and histones. Among more than 100 different modifications identified so far, most of the epitranscriptomics studies focused on the N 6-methyladenosine (m6A), which is the more abundant internal modification in protein coding RNAs. m6A can control several pathways of gene expression, including spicing, export, stability, and translation. In this review, we describe the interplay between m6A and non-coding RNAs, in particular microRNAs and lncRNAs, with examples of its role in gene expression regulation. Finally, we discuss its relevance in cell development and disease.

Keywords: ESC development; RNA modifications; cell reprogramming; epitranscriptomics; lncRNAs; m6A; microRNAs; non-coding RNAs.

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Figures

FIGURE 1

FIGURE 1

Impact of epitranscriptomics on microRNAs biogenesis and function. (A) m6A stimulates microRNA processing by recruiting the Drosha cofactor DGCR8 by the m6A reader HNBRPA2B1 (Alarcón et al., 2015a, b) or, in the case of the miR-126a, by direct interaction with METTL14 (Ma et al., 2017). (B) During aging of peripheral blood mononuclear cells (PBMCs), AGO2 and, eventually, miRNA levels are decreased by higher m6A modification of AGO2 mRNA. This results in enhanced mRNA decay that is very likely mediated by the YTHDF2 reader (Min et al., 2018).

FIGURE 2

FIGURE 2

Examples of the interplay between non-coding RNAs and epitranscriptomics. (A) In glioblastoma stem-like cells (GSCs) the expression of FOXM1 is increased by the concomitant expression of the antisense transcript FOXM1-AS, which, in turn, promote m6A demethylation by recruiting ALKBH5 (Zhang et al., 2017). (B) m6A RNA methylation is positively regulated by microRNAs, which recruit METTL3 on specific mRNA and promotes reprogramming to pluripotency (Chen et al., 2015). (C) m6A modification decreases the IGFBP3 mRNA levels by inhibiting the binding of HuR and promoting the interaction with microRNAs. IGFBP3 protein positively regulates the stability of different developmental regulators. This mechanism ensures low level of IGFBP3 in mESCs (Wang Y. et al., 2014).

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