Vault RNA
Encyclopedia
Vault RNAs are an RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 family found as part of the vault ribonucleoprotein complex first discovered in 1986. The complex consists of a major vault protein
Major vault protein
Major vault protein is a protein that in humans is encoded by the MVP gene.-Interactions:Major vault protein has been shown to interact with Estrogen receptor alpha, PTEN and PARP4.-Further reading:...

(MVP), two minor vault proteins (VPARP
PARP4
Poly [ADP-ribose] polymerase 4 is an enzyme that in humans is encoded by the PARP4 gene.-Interactions:PARP4 has been shown to interact with Major vault protein.-Further reading:...

 and TEP1
TEP1
Telomerase protein component 1 is an enzyme that in humans is encoded by the TEP1 gene.-Further reading:...

), and several small untranslated RNA
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...

 molecules. Each vault particle contains 8-16 vRNA molecules. The vault complex has been linked to drug resistance
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...

. Cryo-electron microscopy
Cryo-electron microscopy
Cryo-electron microscopy , or electron cryomicroscopy, is a form of transmission electron microscopy where the sample is studied at cryogenic temperatures...

 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. It has been shown that TEP1 is involved in stabilising the vRNA.

Species distribution

Vault RNAs have been found in:
  • Human
    Human
    Humans are the only living species in the Homo genus...

  • Rodents
  • Bullfrog
    Bullfrog
    The American bullfrog , often simply known as the bullfrog in Canada and the United States, is an aquatic frog, a member of the family Ranidae, or “true frogs”, native to much of North America. This is a frog of larger, permanent water bodies, swamps, ponds, and lakes, where it is usually found...



Vaults but not the vRNA have also been isolated from:
  • sea urchin
    Strongylocentrotus purpuratus
    The purple sea urchin, Strongylocentrotus purpuratus, lives along the eastern edge of the Pacific Ocean extending from Ensenada, Mexico to British Columbia, Canada. This sea urchin species is deep purple in color and lives in lower intertidal and nearshore subtidal communities...

  • Dictyostelium discoideum
    Dictyostelium discoideum
    Dictyostelium discoideum is a species of soil-living amoeba belonging to the phylum Mycetozoa. D. discoideum, commonly referred to as slime mold, is a eukaryote that transitions from a collection of unicellular amoebae into a multicellular slug and then into a fruiting body within its lifetime. D...

  • Acanthamoeba
    Acanthamoeba
    Acanthamoeba is a genus of amoebae, one of the most common protozoa in soil, and also frequently found in fresh water and other habitats. The cells are small, usually 15 to 35 μm in length and oval to triangular in shape when moving. The pseudopods form a clear hemispherical lobe at the anterior,...


Role in Multidrug Resistance

Vault RNAs, in conjunction with the vault ribonucleoprotein complex, have long been connected with drug resistance, though the mechanisms involved have only recently been determined. Vault non-coding RNAs produce small vault RNAs (svRNAs) through a DICER
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...

 mechanism which then operate in similar manner
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...

 to miRNA
Mirna
Mirna may refer to:geographical entities* Mirna , a river in Istria, Croatia* Mirna , a river in Slovenia, tributary of the river Sava* Mirna , a settlement in the municipality of Mirna in Southeastern Sloveniapeople...

s: an svRNA binds an argonaute
Argonaute
Argonaute proteins are the catalytic components of the RNA-induced silencing complex , the protein complex responsible for the gene silencing phenomenon known as RNA interference . Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs , small interfering RNAs and...

 protein and downregulates expression of CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

, an enzyme involved in drug metabolism
Drug metabolism
Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...

.
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