N6-甲基腺苷
化合物
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]。
| 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。 | |
參考文獻
- ^ 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.
