Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and transcriptional regulation

Abstract

RNA helicases DDX5 and DDX17 are multitasking proteins that regulate gene expression in different biological contexts through diverse activities. Special attention has long been paid to their function as coregulators of transcription factors, providing insight about their functional association with a number of chromatin modifiers and remodelers. However, to date, the variety of described mechanisms has made it difficult to understand precisely how these proteins work at the molecular level, and the contribution of their ATPase domain to these mechanisms remains unclear as well. In light of their association with long noncoding RNAs that are key epigenetic regulators, an emerging view is that DDX5 and DDX17 may act through modulating the activity of various ribonucleoprotein complexes that could ensure their targeting to specific chromatin loci. This review will comprehensively describe the current knowledge on these different mechanisms. We will also discuss the potential roles of DDX5 and DDX17 on the 3D chromatin organization and how these could impact gene expression at the transcriptional and post-transcriptional levels.

Human chromatin remodeler cofactor, RNA interactor, eraser and writer sperm RNAs responding to obesity

“…Similarly, these SREs were enriched in genes responding to the pro-inflammatory cytokine IFN-α [GSE3920, 43], are within the A cluster genes (Figure 1) that steadily increase with BMI, TGF-β1 and IL-6 [GSE39820, 44]. DDX5, a Chromatin remodeler cofactor [73][74][75] (Figure 3, center) belonging to cluster B_II (Figure 1), is an enriched downstream target of both IFN-α and active CD4 + Th1 cells . It increases in response to cyclooxygenase 2 (COX2) [76] and is also associated with pro-inflammatory response [77].…”

Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis

“…DDX5 is an ATP-dependent RNA helicase belonged to the DEAD-box protein family [20]. Previous studies have suggested an important role for DDX5 in regulating transcription in conjunction with multiple, sequence-specific transcription factors [21].…”

DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesis

“…First, they can directly bind to specific RNA substrates, use ATP hydrolysis energy to unwind RNA duplexes, facilitate RNA annealing, and/or organize RNA–protein complex assembly ( 30 , 31 , 32 , 33 ). Second, DDXs can partner with transcription factors to modulate gene transcription ( 24 , 30 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ). In human cancer cell lines, DDX5 interacts with β-catenin protein and the long non-coding RNA NEAT1 to promote oncogene expression ( 41 , 42 ).…”