The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs.

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T1 - The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs.

AU - Persson, Helena

AU - Kvist, Anders

AU - Vallon-Christersson, Johan

AU - Medstrand, Patrik

AU - Borg, Åke

AU - Rovira, Carlos

PY - 2009

Y1 - 2009

N2 - Vault particles are conserved organelles implicated in multidrug resistance and intracellular transport. They contain three different proteins and non-coding vault RNAs (vRNAs). Here we show that human vRNAs produce several small RNAs (svRNAs) by mechanisms different from those in the canonical microRNA (miRNA) pathway. At least one of these svRNAs, svRNAb, associates with Argonaute proteins to guide sequence-specific cleavage and regulate gene expression similarly to miRNAs. We demonstrate that svRNAb downregulates CYP3A4, a key enzyme in drug metabolism. Our findings expand the repertoire of small regulatory RNAs and assign, for the first time, a function to vRNAs that may help explain the association between vault particles and drug resistance.

AB - Vault particles are conserved organelles implicated in multidrug resistance and intracellular transport. They contain three different proteins and non-coding vault RNAs (vRNAs). Here we show that human vRNAs produce several small RNAs (svRNAs) by mechanisms different from those in the canonical microRNA (miRNA) pathway. At least one of these svRNAs, svRNAb, associates with Argonaute proteins to guide sequence-specific cleavage and regulate gene expression similarly to miRNAs. We demonstrate that svRNAb downregulates CYP3A4, a key enzyme in drug metabolism. Our findings expand the repertoire of small regulatory RNAs and assign, for the first time, a function to vRNAs that may help explain the association between vault particles and drug resistance.

U2 - 10.1038/ncb1972

DO - 10.1038/ncb1972

M3 - Article

VL - 11

SP - 1268

EP - 1271

JO - Nature Cell Biology

T2 - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 10

ER -