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The DDX5/Dbp2 subfamily of DEAD-box RNA helicases
Zheng Xing1,2, Wai Kit Ma3, Elizabeth J Tran1,2
1Department of Biochemistry, Purdue University, West Lafayette, Indiana.
Abstract:
The mammalian DEAD-box RNA helicase DDX5, its paralog DDX17, and their orthologs in Saccharomyces cerevisiae and Drosophila melanogaster, namely Dbp2 and Rm62, define a subfamily of DEAD-box proteins. Members from this subfamily share highly conserved protein sequences and cellular functions. They are involved in multiple steps of RNA metabolism including mRNA processing, microRNA processing, ribosome biogenesis, RNA decay, and regulation of long noncoding RNA activities. The DDX5/Dbp2 subfamily is also implicated in transcription regulation, cellular signaling pathways, and energy metabolism. One emerging theme underlying the diverse cellular functions is that the DDX5/Dbp2 subfamily of DEAD-box helicases act as chaperones for complexes formed by RNA molecules and proteins (RNP) in vivo. This RNP chaperone activity governs the functions of various RNA species through their lifetime. Importantly, mammalian DDX5 and DDX17 are involved in cancer progression when overexpressed through alteration of transcription and signaling pathways, meaning that they are possible targets for cancer therapy. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Insights
The DDX5/Dbp2 subfamily of DEAD-box helicases function as RNP chaperones, regulating RNA metabolism and cellular processes. Their roles in cancer progression highlight them as potential therapeutic targets.
Area of Science:
- Molecular Biology
- RNA Metabolism
- Protein-RNA Interactions
Background:
- The DEAD-box RNA helicase DDX5 and its paralog DDX17, along with orthologs Dbp2 and Rm62, form a conserved subfamily.
- This subfamily exhibits conserved protein sequences and cellular functions across species.
- Members are implicated in diverse RNA metabolic processes, including mRNA and microRNA processing, ribosome biogenesis, RNA decay, and lncRNA regulation.
Purpose of the Study:
- To elucidate the conserved cellular functions of the DDX5/Dbp2 subfamily of DEAD-box helicases.
- To highlight the emerging role of this subfamily as in vivo chaperones for RNA-protein complexes (RNPs).
- To underscore the implications of DDX5 and DDX17 in cancer progression and their potential as therapeutic targets.
Main Methods:
- Comparative analysis of conserved protein sequences and cellular functions across species.
- Review of literature detailing the involvement of DDX5/Dbp2 subfamily in RNA metabolism, transcription, signaling, and energy metabolism.
- Investigation of the RNP chaperone activity of the DDX5/Dbp2 subfamily in vivo.
- Analysis of the role of mammalian DDX5 and DDX17 in cancer progression.
Main Results:
- The DDX5/Dbp2 subfamily plays critical roles in multiple RNA metabolism steps and cellular regulation.
- A unifying theme is their function as in vivo chaperones for RNA-protein complexes (RNPs), governing RNA species' functions.
- Overexpression of mammalian DDX5 and DDX17 is linked to cancer progression via altered transcription and signaling.
Conclusions:
- The DDX5/Dbp2 subfamily acts as essential RNP chaperones, crucial for diverse cellular functions.
- Their involvement in cancer progression makes DDX5 and DDX17 promising targets for novel cancer therapies.
- Understanding the RNP chaperone activity provides insights into RNA biology and disease mechanisms.
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