Regulation of the U3-, U8-, and U13snoRNA Expression by the DEAD Box Proteins Ddx5/Ddx17 with Consequences for Cell Proliferation and Survival

Abstract

Small nucleolar RNAs (snoRNAs) in cooperation with their associated proteins (snoRNPs) contribute to the maturation of ribosomal RNA, transfer RNA, and other transcripts. Most snoRNPs mediate chemical base modifications of their RNA substrates, and a few others, like those formed by the C/D snoRNAs U3, U8, and U13, are needed for the structural organization and maturation of primary transcripts. The U3-, U8-, and U13snoRNAs are encoded by autonomous genes, and our knowledge about their expression regulation is limited. In this study, a significant increase in the concentrations of U3-, U8-, and U13snoRNA after a knockdown of DEAD box proteins Ddx5/Ddx17 in HeLa cells is observed. These alterations are shown to be caused by transcriptional suppression mediated by Ddx5/Ddx17 via histone deacetylase 1 in a promoter-dependent way. The biological function of this expression control may be related to the role of Ddx5/Ddx17 in cell proliferation. The U3snoRNA is shown here to be essential for the proliferation and viability of human cells. Moreover, it was found that U3snoRNA interacts with Argonaute 2 in the RNA-induced silencing complexes (RISC), pointing to a microRNA-like function. For this reason, the 3′ untranslated region of the A-kinase anchor protein 9 (AKAP9)-mRNA could be identified as a potential target.