穹窿體RNA
穹窿體RNA（英語：vault RNA，簡稱vRNA）是一種存在於穹窿體核糖核蛋白複合物中的非編碼RNA，該類RNA於1986年被首次發現[1]。作為一種核糖核蛋白複合物，穹窿體除了含有8-16條短鏈RNA外，還包含96個穹窿體主蛋白（major vault proteins，MVP），兩個穹窿體少數蛋白（minor vault proteins，分別為VPARP和TEP1）。穹窿體被認為與抗藥性有關[2][3]。研究人員已利用冷凍顯鏡術揭示出vRNA位於穹窿體「帽」底部的內側。vRNA在穹窿體中的位置可能暗示着穹窿體內外物質都可與其發生相互作用。[4]另有研究發現vRNA需要TEP1以輔助維持自身結構穩定[5]。
| 穹窿體RNA | |
|---|---|
| |
| 穹窿體RNA的二級結構。 | |
| 識別符 | |
| 代號 | vRNA |
| Rfam | RF00701 |
| Entrez | 56664 |
| HUGO | 12654 |
| OMIM | 612695 |
| 其他數據 | |
| RNA類型 | 基因 |
| 域 | 真核生物、脊索動物 |
存在情況
不含vRNA的穹窿體也被從以下幾類生物的細胞中分離：[6]
多藥耐藥作用
結合在穹窿體中的vRNA長期以來都被認為與多藥耐藥有關[2]但直到2009年研究人員才了解其抗藥的機理：穹窿體RNA可以通過DICER機制產生小穹窿體RNA（small vault RNAs ，簡稱svRNA），該機制與作用於miRNA的RNA干擾類，似[3]，當svRNA與一個argonaute蛋白結合後會降低CYP3A4基因的表達，而該基因編碼一種在藥物代謝中需要的酶[7]。
參考文獻
- ^ 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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於2010-12-05）.
擴展閱讀
- 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.
