穹窿体RNA
穹窿体RNA（英语：vault RNA，简称vRNA）是一种存在于穹窿体核糖核蛋白复合物中的非编码RNA，该类RNA于1986年被首次发现[1]。作为一种核糖核蛋白复合物，穹窿体除了含有8-16条短链RNA外，还包含96个穹窿体主蛋白（major vault proteins，MVP），两个穹窿体少数蛋白（minor vault proteins，分别为VPARP和TEP1）。穹窿体被认为与抗药性有关[2][3]。研究人员已利用冷冻显镜术揭示出vRNA位于穹窿体“帽”底部的内侧。vRNA在穹窿体中的位置可能暗示着穹窿体内外物质都可与其发生相互作用。[4]另有研究发现vRNA需要TEP1以辅助维持自身结构稳定[5]。
| 穹窿体RNA | |
|---|---|
| |
| 穹窿体RNA的二级结构。 | |
| 识别符 | |
| 代号 | vRNA |
| Rfam | RF00701 |
| Entrez | 56664 |
| HUGO | 12654 |
| OMIM | 612695 |
| 其他数据 | |
| RNA类型 | 基因 |
| 域 | 真核生物、脊索动物 |
存在情况
不含vRNA的穹窿体也被从以下几类生物的细胞中分离：[6]
多药耐药作用
结合在穹窿体中的vRNA长期以来都被认为与多药耐药有关[2]但直到2009年研究人员才了解其抗药的机理：穹窿体RNA可以通过DICER机制产生小穹窿体RNA（small vault RNAs ，简称svRNA），该机制与作用于miRNA的RNA干扰类，似[3]，当svRNA与一个argonaute蛋白结合后会降低CYP3A4基因的表达，而该基因编码一种在药物代谢中需要的酶[7]。
参考文献
- ^ Kedersha NL, Rome LH. Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA.. J Cell Biol. 1986, 103 (3): 699–709. PMC 2114306
. PMID 2943744. doi:10.1083/jcb.103.3.699.
- ^ 2.0 2.1 Scheffer GL, Wijngaard PLJ, Flens MJ, Izquierdo MA, Slovak M, Meijer C, Clevers HC and Scheper RJ. The Drug Resistance-Related Protein Lrp Is the Human Major Vault Protein. Nature Medicine. 1995, 1 (6): 578–582. PMID 7585126. doi:10.1038/nm0695-578.
- ^ 3.0 3.1 Persson H, Kvist A, Vallon-Christersson J, Medstrand P, Borg A, Rovira C. The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs.. Nat Cell Biol. 2009, 11 (10): 1268–71. PMID 19749744. doi:10.1038/ncb1972.
- ^ Kong LB, Siva AC, Kickhoefer VA, Rome LH, Stewart PL. RNA location and modeling of a WD40 repeat domain within the vault. RNA. 2000, 6 (6): 890–900 [2011-02-04]. PMC 1369965 . PMID 10864046. doi:10.1017/S1355838200000157. （原始内容存档于2019-10-17）.
- ^ Kickhoefer VA, Liu Y, Kong LB; et al. The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle. J. Cell Biol. 2001, 152 (1): 157–64 [2011-02-04]. PMC 2193651 . PMID 11149928. doi:10.1083/jcb.152.1.157. （原始内容存档于2020-05-27）.
- ^ Kedersha NL, Miquel MC, Bittner D, Rome LH. Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes.. J Cell Biol. 1990, 110 (4): 895–901. PMC 2116106 . PMID 1691193. doi:10.1083/jcb.110.4.895.
- ^ Entrez Gene: cytochrome P450. （原始内容存档于2010-12-05）.
扩展阅读
- Subash G, Wadhwa R, Penmetcha KK. Expression of non-coding vault RNA in human malignant cells and its importance in mitoxantrone resistance.. Mol Cancer Res. 2010, 8 (11): 1536–46. PMID 20881010. doi:10.1158/1541-7786.MCR-10-0242.
- Nandy C, Mrázek J, Stoiber H, Grässer FA, Hüttenhofer A, Polacek N. Epstein-barr virus-induced expression of a novel human vault RNA.. J Mol Biol. 2009, 388 (4): 776–84. PMID 19298825. doi:10.1016/j.jmb.2009.03.031.
- Mashima T, Kudo M, Takada Y, Matsugami A, Gopinath SC, Kumar PK, Katahira M. Interactions between antitumor drugs and vault RNA.. Nucleic Acids Symp Ser (Oxf). 2008, 52 (52): 217–8. PMID 18776331. doi:10.1093/nass/nrn110.
- Kickhoefer VA, Emre N, Stephen AG, Poderycki MJ, Rome LH. Identification of conserved vault RNA expression elements and a non-expressed mouse vault RNA gene.. Gene. 2003, 309 (2): 65–70. PMID 12758122. doi:10.1016/S0378-1119(03)00507-9.
- Kickhoefer VA, Poderycki MJ, Chan EK, Rome LH. The La RNA-binding protein interacts with the vault RNA and is a vault-associated protein.. J Biol Chem. 2002, 277 (43): 41282–6. PMID 12196535. doi:10.1074/jbc.M206980200.
- Vilalta A, Kickhoefer VA, Rome LH, Johnson DL. The rat vault RNA gene contains a unique RNA polymerase III promoter composed of both external and internal elements that function synergistically.. J Biol Chem. 1994, 269 (47): 29752–9. PMID 7525587.
- Kickhoefer VA, Searles RP, Kedersha NL, Garber ME, Johnson DL, Rome LH. Vault ribonucleoprotein particles from rat and bullfrog contain a related small RNA that is transcribed by RNA polymerase III.. J Biol Chem. 1993, 268 (11): 7868–73. PMID 7681830.
