The role of m6A RNA methylation in human cancer

Abstract

N 6 -methyladenosine (m 6 A) is identified as the most common, abundant and conserved internal transcriptional modification, especially within eukaryotic messenger RNAs (mRNAs). M 6 A modification is installed by the m 6 A methyltransferases (METTL3/14, WTAP, RBM15/15B and KIAA1429, termed as “writers”), reverted by the demethylases (FTO and ALKBH5, termed as “erasers”) and recognized by m 6 A binding proteins (YTHDF1/2/3, IGF2BP1 and HNRNPA2B1, termed as “readers”). Acumulating evidence shows that, m 6 A RNA methylation has an outsize effect on RNA production/metabolism and participates in the pathogenesis of multiple diseases including cancers. Until now, the molecular mechanisms underlying m 6 A RNA methylation in various tumors have not been comprehensively clarified. In this review, we mainly summarize the recent advances in biological function of m 6 A modifications in human cancer and discuss the potential therapeutic strategies.

Functions of N6-methyladenosine and its role in cancer

“…"Readers" recognize and bind m6A sites, leading to different destinies of target RNA [74,75] (Fig. 2).…”

The interplay between m6A RNA methylation and noncoding RNA in cancer

“…Moreover, there are more than 7000 human genes with 12,000 m6A sites that are enriched in the consensus sequence RRACH (R = G or A and H = A, C, or U), which tends to be found in stop codons and 3′ untranslated regions (3′ UTRs) [12]. M6A modifications occur via the m6A methyltransferases called "writers"; they are removed by the demethylases called "erasers" and are recognized by m6A-binding proteins called "readers" [13][14][15][16]. M6A modifications are quite prevalent, and the dynamic regulation of m6A modifications has been shown to be significantly related to gene expression [17][18][19][20][21][22].…”

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

“…m 6 A is enriched in stop codon and 3′ untranslated terminal region (UTR) and translates near 5′ UTR in a cap-independent manner [4][5][6], thereby regulating RNA transcription, translation, processing and metabolism [5,6]. The process of m 6 A modification is reversible and can be regulated by three homologous factors jargonized as 'writers' , 'erasers' and 'readers' [7,8]. For example, 'Writers' are categorized as the components of that catalyze the formation of m 6 A methylation [7,9]; 'Erasers' play an important role in m 6 A modification for their demethylated functions [10,11]; 'Readers' are a group of molecules which can decode m 6 A methylation and generate functional signals [12,13].…”