Redundant role of DEAD box proteins p68 (Ddx5) and p72/p82 (Ddx17) in ribosome biogenesis and cell proliferation

Abstract

The DEAD box proteins encoded by the genes ddx5 (p68) and ddx17 (isoforms p72 and p82) are more closely related to each other than to any other member of their family. We found that p68 negatively controls p72/p82 gene expression but not vice versa. Knocking down of either gene does not affect cell proliferation, in case of p68 suppression, however, only on condition that p72/p82 overexpression was granted. In contrast, co-silencing of both genes causes perturbation of nucleolar structure and cell death. In mutant studies, the apparently redundant role(s) of p68 and p72/p82 correspond to their ability to catalyze RNA rearrangement rather than RNA unwinding reactions. In search for possible physiological targets of this RNA rearrangement activity it is shown that the nucleolytic cleavage of 32S pre-rRNA is reduced after p68 subfamily knock-down, most probably due to a failure in the structural rearrangement process within the pre-60S ribosomal subunit preceding the processing of 32S pre-rRNA.

Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA

“…p68 is required for ribosome biogenesis, and its ATPase/helicase activities are important for premRNA splicing and microRNA processing (Lin et al 2005;Jalal et al 2007;Salzman et al 2007). Notably, p68 is an essential component of the Drosha complex (Fukuda et al 2007).…”

Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

“…Drosha localizes to the nucleus and also transits into the nucleolus during S phase 32 . Mouse embryos deficient for either Ddx5 or Ddx17 have reduced levels of 5.8S rRNA and most miRNAs, and this phenotype can be reproduced using siRNAs that target Ddx5, Ddx17 or Drosha in MEFs and HeLa cells 19,33 . Considering the dual involvement of Eri1, Drosha, Ddx5 and Ddx17 in rRNA processing and the RNAi pathway, one may speculate that, during evolution, factors that were primarily involved in rRNA processing later acquired new functions in the biogenesis and regulation of short regulatory RNA molecules.…”

The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis

“…Acting as RNA chaperones, they seem to support virtually all RNA-related processes (Linder, 2006). Ddx5 and its close relative Ddx17 (isoforms p72 and p82; UhlmannSchiffler et al, 2002) are truly outstanding with respect to the diversity of their physiological functions (Ishizuka et al, 2002;Ho¨ck et al, 2007;Jalal et al, 2007), including those that seem not to require their RNAspecific activity (reviewed in Fuller-Pace, 2006).…”