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

Vault particles are conserved organelles that have been implicated in multidrug resistance and intracellular transport. They are formed by three different proteins and the non-coding vault RNAs (vRNAs). Here we show that human vRNAs produce several small RNAs (svRNAs) by mechanisms different from the canonical microRNA (miRNA) pathway. At least one of these svRNAs, we named svRNAb, associates with Argonaute proteins to guide sequence-specific cleavage and regulate gene expression in a manner similar 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 observed association between vaults and drug resistance. Keywords: Transcriptome analysis Overall design: Small RNAs 18-35 nt were isolated from MCF7 cell total RNA and sequenced on the Illumina Genome Analyzer