| Summary: | Vault RNA are small non-coding polymerase III transcribed RNA, which are a crucial com- ponent of a large ribonucleoprotein complex called Vault. Despite only 5% of vault RNA being associated with the Vault complex, little is known about their Vault-independent cellular roles. Here I show that vtRNA are processed by Dicer into functional small vault RNA (svtRNA) fragments that associate with Argonaute 2. Nascent RNA sequencing revealed the highest number of predicted svtRNA1-2 target genes among up-regulated genes, in AGO2 and Dicer Knock Down cells, compared to other svtRNA. svtRNA1-2 target sites were detected predominantly in the intronic regions. Genomic deletion of vtRNA1-2 results in the severe inhibition of proliferation and up-regulation of genes sig- nificantly associated with cell membrane physiology, including ERBB4 and cell adhesion. Finally, I show that svtRNA1-2 hybridises to target genes in a dual-region complemen- tarity and loop protrusion is required for intron targeting. These results show a novel small vault RNA1-2 with a role in gene expression regulation, possessing unique molecular features for targeting genes in introns leading to nascent RNA silencing.
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