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N6-methyladenosine (m6A)

N6-甲基腺苷
Catalog No.
B5993
腺苷酸环化酶的调节剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 454.00
现货
100mg
¥ 727.00
现货
500mg
¥ 1,363.00
现货

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A

背景

N6-methyladenosine (m6A或N6m)是一种腺苷激动剂,ED50值为17.250 μM[1],是腺苷酸环化酶的调节剂[2]。在所有高等真核生物中作为信使RNA(mRNA)的修饰剂,它是mRNA最常见的内部(非帽)修饰,它参与mRNA的稳定性的调节[3]。

腺苷酸环化酶催化ATP形成环化腺苷3',5'-单磷酸(cAMP)[4]。在Calu-6细胞中,cAMP增加了人类肾素mRNA的稳定性[5]。

N6m以浓度依赖性方式防止血红蛋白的积累,抑制终端成熟的起始反应。N6m减缓细胞生长速度,但它基本上没有抑制DNA合成及显著降低MEL细胞的活力和克隆潜力。在MEL细胞中,N6m降低细胞质中积累的β球蛋白的mRNA,影响该mRNA的结构完整性。腺嘌呤、L-高半胱氨酸和/或L-蛋氨酸加强了N6m诱导的起始抑制。腺嘌呤、L-高半胱氨酸和L-蛋氨酸都参与了活化的甲基化周期[6]。

在哺乳动物中,RNA m6A修饰优先发生在3'UTRs和基因编码区的共有序列RRACH内(R = G或A; H = A、C或U),这意味着m6A起到了调节RNA的加工和翻译的基础作用[7]。

参考文献:
[1].  Ribeiro JA and Sebastio AM. On the type of receptor involved in the inhibitory action of adenosine at the neuromuscular junction. Br J Pharmacol, 1985, 84(4):911-8.
[2].  Londos C, Wolff J and Cooper DMF. Adenosine as a regulator of adenylate cyclase[M]//Purinergic receptors. Springer Netherlands, 1981:287-323.
[3].  Wang X, Lu Z, Gomez A, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 2014, 505(7481): 117-120.
[4].  Salomon Y, Londos C and Rodbell M. A highly sensitive adenylate cyclase assay. Analytical biochemistry, 1974, 58(2): 541-548.
[5].  Sinn P L and Sigmund CD. Human renin mRNA stability is increased in response to cAMP in Calu-6 cells. Hypertension, 1999, 33(3): 900-905. [6]. Vizirianakis IS, Wong W and Tsiftsoglou AS. Analysis of the inhibition of commitment of murine erythroleukemia (MEL) cells to terminal maturation by N 6-methyladenosine. Biochemical pharmacology, 1992, 44(5): 927-936.
[7].  Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell research, 2014, 24(12): 1403-1419.

文献引用

化学属性

Physical AppearanceA solid
StorageStore at -20°C
M.Wt281.27
Cas No.1867-73-8
FormulaC11H15N5O4
Solubilityinsoluble in H2O; ≥12.2 mg/mL in DMSO; ≥2.73 mg/mL in EtOH with gentle warming and ultrasonic
Chemical Name(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol
SDFDownload SDF
Canonical SMILESCNC1=C(N=CN2[C@@]3([H])[C@@](O)([H])[C@@](O)([H])[C@@](O3)([H])CO)C2=NC=N1
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试验操作

Cell experiment:[1]

Cell lines

Murine erythroleukemia (MEL) cells

Reaction Conditions

0 ~ 10-3 M N6m for 96 h incubation

Applications

N6m exerted a concentration dependent inhibitory effect on MEL cell differentiation in the presence of DMSO. The maximum degree of inhibition of MEL cell differentiation was observed at 0.5 mM as shown by the accumulation of differentiated cells and hemoglobin content. In addition, the inhibitory effect of N6m on MEL cell differentiation was not specific to DMSO. N6m was able to inhibited MEL cell differentiation induced by a number of structurally unrelated inducers incuding butyric acid, hypoxanthine, UDP-4, DMA and HMBA.

Note

The technical data provided above is for reference only.

References:

1. Vizirianakis IS, Wong W, Tsiftsoglou AS. Analysis of the inhibition of commitment of murine erythroleukemia (MEL) cells to terminal maturation by N6-methyladenosine. Biochemical Pharmacology, 1992, 44(5): 927-936.

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