Non-sense-mediated mRNA decay (NMD) is a mechanism of translation-dependent mRNA surveillance in eukaryotes: it degrades mRNAs with premature termination codons (PTCs) and contributes to cellular homeostasis by downregulating a number of physiologically important mRNAs. In the NMD pathway, Upf proteins, a set of conserved factors of which Upf1 is the central regulator, recruit decay enzymes to promote RNA cleavage. In mammals, the degradation of PTC-containing mRNAs is triggered by the exon–junction complex (EJC) through binding of its constituents Upf2 and Upf3 to Upf1. The complex formed eventually induces translational repression and recruitment of decay enzymes. Mechanisms by which physiological mRNAs are targeted by the NMD machinery in the absence of an EJC have been described but still are discussed controversially. Here, we report that the DEAD box proteins Ddx5/p68 and its paralog Ddx17/p72 also bind the Upf complex by physical interaction with Upf3, thereby interfering with the binding of EJC. By activating the NMD machinery, Ddx5 is shown to regulate the expression of its own, Ddx17 and Smg5 mRNAs. For NMD triggering, the adenosine triphosphate-binding activity of Ddx5 and the 3′-untranslated region of substrate mRNAs are essential.

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.