Disease relevance of N-Methyladenosine

• The activity in the SCID patient was inhibitable by 2-fluoroadenosine and N6-methyladenosine, known competitive inhibitors of human red cell adenosine deaminase [1].
• Role of N6-methyladenosine in expression of Rous sarcoma virus RNA: analyses utilizing immunoglobulin specific for N6-methyladenosine [2].
• Unequal distribution of N6-methyladenosine in influenza virus mRNAs [3].
• Localization of six new N6-methyladenosine sites on Rous sarcoma virus (RSV) virion RNA has confirmed our extended consensus sequence for methylation: RGACU, where R is usually a G (7/12) [4].
• Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA [5].

High impact information on N-Methyladenosine

• Mapping of N6-methyladenosine residues in bovine prolactin mRNA [6].
• Influenza virus mRNA is posttranscriptionally methylated at internal adenosine residues to form N6-methyladenosine (m6A) [3].
• Wheat germ cytoplasmic ribosomes. Localization of 7-methylguanosine and 6-methyladenosine by electron microscopy of immune complexes [7].
• Nucleoside analysis of the RNA from the small subunit of wheat germ cytoplasmic ribosomes shows 1 mol each of N7-methylguanosine and N6-methyladenosine/mol of RNA [7].
• Inhibition of methylation at two internal N6-methyladenosine sites caused by GAC to GAU mutations [8].

Biological context of N-Methyladenosine

• A base-methylated nucleoside, N6-methyladenosine, is located within the RNA chain and is released as a mononucleotide by alkali hydrolysis [9].
• Localization of N6-methyladenosine in the Rous sarcoma virus genome [10].
• Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid [11].
• While 48.6% of the [3H]methyl radioactivity was present as N6-methyladenosine in poly(adenylic acid)-terminated mRNA from S-phase cells, no evidence for N6-methyladenosine was found in histone mRNA [12].
• These findings indicate that N6-methyladenosine: (a) blocks a central process that is required for initiation of commitment; and (b) decreases accumulation of beta (major) globin mRNA, causes mRNA degradation and prevents hemoglobin synthesis [13].

Anatomical context of N-Methyladenosine

• A T7 RNA transcript coding for mouse dihydrofolate reductase (DHFR) was utilized as a substrate for the N6-methyladenosine mRNA methyltransferase isolated from HeLa cell nuclei [14].
• Effects of N6-methyladenosine on the synthesis of phenylethanolamine N-methyltransferase in cultured explants of rat adrenal medulla [15].
• N6-Methyladenosine strongly stimulates [1-14C]glucose oxidation in rat adipocytes [J.E. Souness and V. Chagoya de Sanchez, Fedn Eur. Biochem. Soc. Lett. 125, 249 (1981)] [16].
• Cells cultured in cycloleucine produced transcripts deficient in N6-methyladenosine residues and the 2'-O-methylated nucleosides of the cap structure; however, the formation of the 7-methylguanine nucleoside of the cap was not effected [17].
• Adenosine and its analogues, but not N6-methyladenosine, protected erythrocytes against hypotonic haemolysis in a concentration-dependent manner [18].

Associations of N-Methyladenosine with other chemical compounds

• This paper demonstrates that N6-methyladenosine (6-methylaminopurine ribonucleoside) will condense in vitro with homocysteine to form S-N6-methyladenosylhomocysteine in a reaction catalyzed by mouse liver S-adenosylhomocysteine hydrolase [19].
• The quantitative modification of these two nucleosides in the presence of guanosine may be achieved with high selectivity only at a low pH of 3.0--4.0 N6-methyladenosine and N4-methylcytidine react quantitatively with chloroacetaldehyde and the reaction rate is higher than in the case of the parent nucleosides [20].
• From the determined values for the extent of methylation of 4S RNA isolated from infected chicken embryo cells, it was estimated that 30 to 40S RNA subunits that results from heat denaturation of the 60 to 70S RNA contain approximately 21 methyl groups, of which 14 to 16 are present at internal positions as N6 -methyladenosine residues [21].
• The methylation of internal adenosine residues in eukaryotic mRNA, forming N6-methyladenosine (m6A), is catalyzed by a complex multicomponent enzyme [22].
• Kinetics experiments demonstrated that N6-methyladenosine is a competitive inhibitor of hypoxanthine uptake with a Ki of 30 uM [23].

Gene context of N-Methyladenosine

• Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene [24].
• MEL cells that failed to differentiate from treatment with N(6)-methyladenosine (N(6)mAdo), an inhibitor of differentiation, were also analyzed for PrP mRNA level [25].
• The results are consistent with the view that this effect of N6-methyladenosine on the concentration of phenylethanolamine N-methyltransferase is due to an inhibition of its biosynthesis rather than to an alteration of its rate of degradation [15].
• The only internal methylated nucleoside, N6-methyladenosine (m6A), was found exclusively as m6ApC and Apm6ApC after digestion with RNase A, T1, and alkaline phosphatase [26].
• Decrease in tyrosine hydroxylase synthesis in cultured adrenal medulla by N6-methyladenosine [27].

Analytical, diagnostic and therapeutic context of N-Methyladenosine

• The salient feature of the method is the combined usage of antibodies against 2,2,7-trimethylguanosine (m3G) and 6-methyladenosine (m6A) for differential immune affinity chromatography of the snRNPs [28].
• High performance liquid chromatography revealed a fifth base, in addition to the four nucleosides, which was identified as N6-methyladenosine [29].
• Borate gel chromatography was used to separate internal oligonucleotides containing N6-methyladenosine (m6A) from methylated 5'-terminal oligonucleotides of HeLa cell polyadenylylated mRNA [11].

References