mRNA decay mediated by the DEAD-box RNA helicase Ddx5

The DEAD-box RNA helicases Ddx5 and Ddx17 (alias: p68 and p72) are paralogs with similar biochemical activities and partially overlapping functions in cell growth, differentiation and carcinogenesis. The control of their own expression is poorly understood. Here we identify a posttranscriptional mechanism, which reduces the level of Ddx17 in response to the intracellular concentration of Ddx5. This cross regulation results in strongly decreased steady-state levels of Ddx17 mRNA. It requires ATP hydrolysis of the Ddx5 RNA helicase and the support of Upf (up-frameshift factor)1, 2, and 3, crucial for nonsense-mediated mRNA decay (NMD). In fact, we demonstrate that in HeLa cells Ddx5, like its homolog Dbp2p in yeast, physically interacts with Upf1. However, unlike Dpb2p, Ddx5 is not an essential factor of the premature termination codon-dependent NMD in mammalian cells.