The small non-coding RNAVaultrc5is dispensable to mouse development

Abstract

ABSTRACTVault RNAs (vRNAs) are evolutionarily conserved small non-coding RNAs transcribed by RNA polymerase lll. Initially described as components of the vault particle, they have since also been described as noncanonical miRNA precursors and as riboregulators of autophagy. As central molecules in these processes, vRNAs have been attributed numerous biological roles including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAsin vivo,we generated a mouse line with a conditionalVaultrc5loss of function allele. BecauseVaultrc5is the sole murine vRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null forVaultrc5are viable and histologically normal but have a slight reduction in platelet counts pointing to a potential role for vRNAs in hematopoiesis. This work paves the way for furtherin vivocharacterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specificVaultrc5deletion and of the physiological requirements for an intactVaultrc5during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.