N6-甲基腺苷
化合物
N6-甲基腺苷（N6-Methyladenosine，简称m6A）是真核生物细胞mRNA中最常见的修饰，也见于tRNA、rRNA、snRNA和lncRNA（如Xist）等其他种RNA，细胞RNA中约有0.1%至0.4%的腺苷（A）位点具有此修饰[1]。m6A最早在1970年代即被发现，但未知其功能[2][3]，近年随着其修饰酶（writer）、去修饰酶（eraser）和识别蛋白（reader）的发现，其修饰机制与功能逐渐明朗。m6A是由一甲基转移酶复合体修饰，复合体包括METTL3、METTL14、WTAP、RBM15、KIAA1429与METTL5等，可将S-腺苷甲硫氨酸（SAM）上的甲基转移到RNA的腺苷上[1]；FTO蛋白与ALKBH5则为m6A去甲基酶，可移除RNA上m6A的甲基[1]；具YTH结构域（YT521-B homology domain）的蛋白（YTHDF1、YTHDF2、YTHDF3和YTHDC1等）、IGF2BP1、IGF2BP2、IGF2BP3、FMR1和RBMX等蛋白可与mRNA上的m6A结合，为其识别蛋白，因蛋白种类和RNA序列而异可促进或抑制其翻译、降解、剪接等[1]。研究m6A转录组的技术包括m6A测序（m6A Seq ）、mRNA甲基化测序（MeRIP-seq）、m6A-CLIP与SCARLET等[1]。有数种癌症与m6A修饰的异常有关[4][5][6]。除真核生物外，许多RNA病毒也具有m6A修饰，可能与其感染、复制有关[7][8][9]。
| N6-甲基腺苷 | |
|---|---|
| |
| IUPAC名 N-Methyladenosine | |
| 别名 | m6A |
| 识别 | |
| CAS号 | 1867-73-8 
|
| PubChem | 102175 |
| ChemSpider | 92307 |
| SMILES |
|
| 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。 | |
参考文献 编辑
- ^ 1.0 1.1 1.2 1.3 1.4 Zhang C, Fu J, Zhou Y. A Review in Research Progress Concerning m6A Methylation and Immunoregulation.. Front Immunol. 2019, 10: 922. PMC 6497756
. PMID 31080453. doi:10.3389/fimmu.2019.00922.
- ^ 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.
- ^ Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proceedings of the National Academy of Sciences of the United States of America. 1974, 71 (10): 3971–5. Bibcode:1974PNAS...71.3971D. PMC 434308 . PMID 4372599. doi:10.1073/pnas.71.10.3971.
- ^ Akilzhanova A, Nurkina Z, Momynaliev K, Ramanculov E, Zhumadilov Z, Zhumadilov Z, Rakhypbekov T, Hayashida N, Nakashima M, Takamura N. Genetic profile and determinants of homocysteine levels in Kazakhstan patients with breast cancer. Anticancer Research. 2013, 33 (9): 4049–59. PMID 24023349.
- ^ Reddy SM, Sadim M, Li J, Yi N, Agarwal S, Mantzoros CS, Kaklamani VG. Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer (PDF). British Journal of Cancer. 2013, 109 (4): 872–81 [2021-05-03]. PMC 3749587 . PMID 23922112. doi:10.1038/bjc.2013.441. （原始内容存档 (PDF)于2021-05-03）.
- ^ Heiliger KJ, Hess J, Vitagliano D, Salerno P, Braselmann H, Salvatore G, Ugolini C, Summerer I, Bogdanova T, Unger K, Thomas G, Santoro M, Zitzelsberger H. Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice. Endocrine-Related Cancer. 2012, 19 (3): 409–21. PMID 22454401. doi:10.1530/ERC-11-0387.
- ^ 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.
