Methylation of mRNA

Narayan, Prema; Rottman, Fritz M.

doi:10.1002/9780470123119.ch7

Cited by 19 publications

(15 citation statements)

References 96 publications

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“…RNA m 6 A is widely conserved across plants 9–12 and vertebrates 2,3,13–18 , and is also found in viruses 19–23 as well as in single-cell organisms such as archaea 24,25 , bacteria 26 and yeast 27 (Supplementary information S1 (box)). The amount of m 6 A in isolated RNA is estimated to constitute 0.1–0.4% of all adenosine nucleotides in mammals 18,28 , 0.7–0.9% of adenine nucleotides (all within GA dinucleotides) in meiotic Saccharomyces cerevisiae 29 , and 1–15 sites per virion RNA molecule in various viruses 30 . Mutation and in vitro enzymatic studies have identified a consensus motif of RRm 6 ACH ([G/A/U][G>A]m 6 AC[U>A>C]) 31–34 .…”

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confidence: 99%

Post-transcriptional gene regulation by mRNA modifications

Zhao

Roundtree

2016

Nat Rev Mol Cell Biol

1,748

1,747

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The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N6-methyladenosine (m6A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses. Other mRNA modifications, including N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome and collectively code a new layer of information that controls protein synthesis.

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confidence: 99%

Post-transcriptional gene regulation by mRNA modifications

Zhao

Roundtree

2016

Nat Rev Mol Cell Biol

1,748

1,747

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“…Betaine provides methyl group for the transformation of homocysteine to methionine, which serves as a substrate for the synthesis of SAM. Importantly, SAM is the major methyl group donator not only for DNA methylation but also for mRNA m 6 A methylation [4,19]. Similar to methyl modification in DNA, mRNA also undergoes posttranscriptional methylation to regulate its fate and function [18].…”

Section: Discussionmentioning

confidence: 99%

“…Betaine (trimethylglycine) serves as a substrate for the formation of methionine and could be further converted to S-adenosylmethionine (SAM) [16]. SAM is the major methyl group donator for DNA methylation and N6-methyladenosine (m 6 A) mRNA methylation [4,19]. So far, the effects of betaine on the modulation of gene expression through modifying epigenetic marks such as DNA methylation have been reported [7].…”

Section: Introductionmentioning

confidence: 98%

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

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“…mRNAs isolated from lower eukaryotes such as S. cerevisiae (Sri-pati et al 1976), Dictyostelium (Dottin et al 1976), and Neurospora (Seidel and Somberg 1978) were traditionally thought to not contain detectable amounts of m 6 A, although it is now known that m 6 A is present in S. cerevisiae mRNA isolated from yeast growing meiotically, but not mitotically (this will be discussed in detail below). This modification is present in viral RNAs that replicate in the nucleus (adenovirus, SV40, herpes viruses, Rous sarcoma virus, influenza) (Somner et al 1976;Aloni et al 1979;Canaani et al 1979;Bartuski and Roizman 1978;Beemon and Keith 1977;Narayan et al 1987), but not in the RNA from viruses that do not have a nuclear phase in their life cycle (Sindbis virus, vaccinia, reovirus, vesicular stomatitis virus) (for review see Narayan and Rottman 1992). Analysis of the methylated constituents of mouse L cell, Novikoff hepatoma cell, and HeLa cell mRNA has revealed that approximately 50% of incorporated methyl label is in m 6 A ( Fig.…”

Section: N6-methyladenosinementioning

confidence: 97%

The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA

Bokar

2005

Fine-Tuning of RNA Functions by Modification and Editing

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Modified nucleosides are present in mRNA of all eukaryotes, albeit at much lower levels than in other RNA moieties such as rRNA, tRNA, and snRNA. Modification by methylation occurs on the terminal guanosine of the cap (N 7 -methylguanosine), and the first two encoded nucleosides (2'-O-methylnuculeosides) in most higher eukaryotes. Additional modifications of cap nucleosides occur in special cases where the cap is derived by trans-splicing in nematodes and kinetoplastids. Modification by methylation also occurs at internal adenosine residues in many species (N 6 -methyladenosine). Modification by deamination occurs at specific adenosine residues (forming inosine) and cytidine residues (forming uridine) in very specific cases leading to post-transcriptional editing. Numerous studies have shown the importance of the cap N 7 -methylguanosine in translation, splicing, transport, and mRNA stability. The role of the 2'-O-methylnucleosides is not as well understood, but there is evidence that these modifications play some role in translation efficiency. The role of internal N 6 -methyladenosine residues is least known, and is the focus of this review. The formation of N 6 -methyladenosine is catalyzed by a complex enzyme containing a subunit (MT-A70) that co-localizes with nuclear speckles and appears to be widely expressed in all higher eukaryotes. Loss of this enzyme leads to a sporulation defect in yeast and to apoptosis in mammalian cells, although the exact mechanism by which the effects occur remains obscure.

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Methylation of mRNA

Cited by 19 publications

References 96 publications

Post-transcriptional gene regulation by mRNA modifications

Post-transcriptional gene regulation by mRNA modifications

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA

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