Vault RNA

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Vault RNA
Vault RNA secondary structure.png
Vault RNA secondary structure and sequence conservation.
Identifiers
Symbol vRNA (also vtRNA)
Rfam RF00006
Entrez 56664
HUGO 12654
OMIM 612695
Other data
RNA type Gene
Domain(s) Eukaryota; Chordata;

Vault RNAs (vRNA, also known as vtRNA) are an RNA family found as part of the vault ribonucleoprotein complex first discovered in 1986.[1] The complex consists of a major vault protein (MVP), two minor vault proteins (VPARP and TEP1), and several small untranslated RNA molecules. Each vault particle contains 8-16 vRNA molecules. The vault complex has been linked to drug resistance.[2][3] Cryo-electron microscopy has revealed the vRNA resides internally close to the ends of the vault caps. The position of vRNA suggests that it could interact with both the interior and exterior of the vault particle.[4] It has been shown that TEP1 is involved in stabilising the vRNA.[5] It has been shown that vault RNAs contain multiple cytosine residues that are methylated by the NSUN2 protein.[6] Loss of cytosine-5 methylation in NSUN2 deficient cells causes incorrect processing into small RNA fragments. It has been suggested that impaired vault RNA processing may contribute to NSUN2 deficiency diseases.

Species distribution[edit]

Vault RNAs have been found in:[citation needed]

Vaults but not the vRNA have also been isolated[7] from:

Role in multidrug resistance[edit]

Vault RNAs, in conjunction with the vault ribonucleoprotein complex, have long been connected with drug resistance,[2] though the mechanisms involved have only recently been determined. Vault non-coding RNAs produce small vault RNAs (svRNAs) through a DICER mechanism which then operate in similar manner to miRNAs:[3] an svRNA binds an argonaute protein and downregulates expression of CYP3A4, an enzyme involved in drug metabolism.[8]

See also[edit]

References[edit]

  1. ^ Kedersha NL, Rome LH (1986). "Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA". J Cell Biol 103 (3): 699–709. doi:10.1083/jcb.103.3.699. PMC 2114306. PMID 2943744. 
  2. ^ a b Scheffer GL, Wijngaard PLJ, Flens MJ, Izquierdo MA, Slovak M, Meijer C, Clevers HC and Scheper RJ (1995). "The Drug Resistance-Related Protein Lrp Is the Human Major Vault Protein". Nature Medicine 1 (6): 578–582. doi:10.1038/nm0695-578. PMID 7585126. 
  3. ^ a b Persson H, Kvist A, Vallon-Christersson J, Medstrand P, Borg A, Rovira C (2009). "The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs". Nat Cell Biol 11 (10): 1268–71. doi:10.1038/ncb1972. PMID 19749744. 
  4. ^ Kong LB, Siva AC, Kickhoefer VA, Rome LH, Stewart PL (2000). "RNA location and modeling of a WD40 repeat domain within the vault". RNA 6 (6): 890–900. doi:10.1017/S1355838200000157. PMC 1369965. PMID 10864046. 
  5. ^ Kickhoefer VA, Liu Y, Kong LB et al. (2001). "The Telomerase/Vault-Associated Protein Tep1 Is Required for Vault RNA Stability and Its Association with the Vault Particle". J. Cell Biol. 152 (1): 157–64. doi:10.1083/jcb.152.1.157. PMC 2193651. PMID 11149928. 
  6. ^ Hussain, S; Sajini, AA; Blanco, S; Dietmann, S; Lombard, P; Sugimoto, Y; Paramor, M; Gleeson, JG; Odom, DT; Ule, J; Frye, M (2013). "NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs". Cell reports 4 (2): 255–61. doi:10.1016/j.celrep.2013.06.029. PMC 3730056. PMID 23871666. 
  7. ^ Kedersha NL, Miquel MC, Bittner D, Rome LH (1990). "Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes". J Cell Biol 110 (4): 895–901. doi:10.1083/jcb.110.4.895. PMC 2116106. PMID 1691193. 
  8. ^ "Entrez Gene: cytochrome P450". 

Further reading[edit]

[1] [2] [3] [4] [5] [6] [7]

  1. ^ Subash G, Wadhwa R, Penmetcha KK (2010). "Expression of non-coding vault RNA in human malignant cells and its importance in mitoxantrone resistance". Mol Cancer Res 8 (11): 1536–46. doi:10.1158/1541-7786.MCR-10-0242. PMID 20881010. 
  2. ^ Nandy C, Mrázek J, Stoiber H, Grässer FA, Hüttenhofer A, Polacek N (2009). "Epstein-barr virus-induced expression of a novel human vault RNA". J Mol Biol 388 (4): 776–84. doi:10.1016/j.jmb.2009.03.031. PMID 19298825. 
  3. ^ Mashima T, Kudo M, Takada Y, Matsugami A, Gopinath SC, Kumar PK, Katahira M (2008). "Interactions between antitumor drugs and vault RNA". Nucleic Acids Symp Ser (Oxf) 52 (52): 217–8. doi:10.1093/nass/nrn110. PMID 18776331. 
  4. ^ Kickhoefer VA, Emre N, Stephen AG, Poderycki MJ, Rome LH (2003). "Identification of conserved vault RNA expression elements and a non-expressed mouse vault RNA gene". Gene 309 (2): 65–70. doi:10.1016/S0378-1119(03)00507-9. PMID 12758122. 
  5. ^ Kickhoefer VA, Poderycki MJ, Chan EK, Rome LH (2002). "The La RNA-binding protein interacts with the vault RNA and is a vault-associated protein". J Biol Chem 277 (43): 41282–6. doi:10.1074/jbc.M206980200. PMID 12196535. 
  6. ^ Vilalta A, Kickhoefer VA, Rome LH, Johnson DL (1994). "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 269 (47): 29752–9. PMID 7525587. 
  7. ^ Kickhoefer VA, Searles RP, Kedersha NL, Garber ME, Johnson DL, Rome LH (1993). "Vault ribonucleoprotein particles from rat and bullfrog contain a related small RNA that is transcribed by RNA polymerase III". J Biol Chem 268 (11): 7868–73. PMID 7681830. 

External links[edit]