N6-甲基腺苷
N6-甲基腺苷 | |
---|---|
IUPAC名 N-Methyladenosine | |
别名 | m6A |
识别 | |
CAS号 | 1867-73-8 |
PubChem | 102175 |
ChemSpider | 92307 |
SMILES |
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ChEBI | 21891 |
性质 | |
化学式 | C11H15N5O4 |
摩尔质量 | 281.27 g·mol−1 |
若非注明,所有数据均出自标准状态(25 ℃,100 kPa)下。 |
N6-甲基腺苷(N6-Methyladenosine,簡稱m6A)是真核生物細胞mRNA中最常見的修飾,也見於tRNA、rRNA、snRNA和lncRNA(如Xist)等其他種RNA,細胞RNA中約有0.1%至0.4%的腺苷(A)位點具有此修飾[1]。m6A最早在1970年代即被發現,但未知其功能[2][3],近年隨著其修飾酶(writer)、去修飾酶(eraser)和識別蛋白(reader)的發現,其修飾機制與功能逐漸明朗。m6A是由一甲基轉移酶複合體修飾,複合體包括METTL3、METTL14、WTAP、RBM15、KIAA1429與METTL5等,可將S-腺苷甲硫氨酸(SAM)上的甲基轉移到RNA的腺苷上[1];FTO蛋白與ALKBH5則為m6A去甲基酶,可移除RNA上m6A的甲基[1];具YTH結構域(YT521-B homology domain)的蛋白(YTHDF1、YTHDF2、YTHDF3和YTHDC1等)、IGF2BP1、IGF2BP2、IGF2BP3、FMR1和RBMX等蛋白可與mRNA上的m6A結合,為其識別蛋白,因蛋白種類和RNA序列而異可促進或抑制其轉譯、降解、剪接等[1]。研究m6A轉錄組的技術包括m6A測序(m6A Seq )、mRNA甲基化测序(MeRIP-seq)、m6A-CLIP與SCARLET等[1]。有數種癌症與m6A修飾的異常有關[4][5][6]。除真核生物外,許多RNA病毒也具有m6A修飾,可能與其感染、複製有關[7][8][9]。
參考文獻
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- ^ Adams JM, Cory S. Modified nucleosides and bizarre 5'-termini in mouse myeloma mRNA. Nature. 1975, 255 (5503): 28–33. Bibcode:1975Natur.255...28A. PMID 1128665. doi:10.1038/255028a0.
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- ^ Kennedy EM, Bogerd HP, Kornepati AV, Kang D, Ghoshal D, Marshall JB, Poling BC, Tsai K, Gokhale NS, Horner SM, Cullen BR. Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression. Cell Host & Microbe. May 2016, 19 (5): 675–85. PMC 4867121 . PMID 27117054. doi:10.1016/j.chom.2016.04.002.
- ^ Tirumuru N, Zhao BS, Lu W, Lu Z, He C, Wu L. N(6)-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression. eLife. 2016, 5. PMC 4961459 . PMID 27371828. doi:10.7554/eLife.15528.
- ^ Lichinchi G, Gao S, Saletore Y, Gonzalez GM, Bansal V, Wang Y, Mason CE, Rana TM. Dynamics of the human and viral m(6)A RNA methylomes during HIV-1 infection of T cells. Nature Microbiology. 2016, 1 (4): 16011. PMC 6053355 . PMID 27572442. doi:10.1038/nmicrobiol.2016.11.