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DEAH-box helicase 8 (DHX8)
- Target
- DHX8
- Molecular classification
- Enzyme, ATP-dependent RNA helicase, DEAH box protein family, Spliceosome-associated protein
01
Overview
DEAH-box helicase 8 is an ATP-dependent RNA helicase and a core component of the spliceosome, responsible for the critical step of releasing mature, spliced mRNAs from the spliceosome to the nucleus prior to their export into the cytoplasm. This protein contains characteristic DEAH (Asp-Glu-Ala-His) motifs and multiple structured and intrinsically disordered domains, including S1 RNA-binding, helicase, HA2, and OB-fold domains. DHX8 is essential in pre-mRNA splicing, promoting proper gene expression, particularly under conditions of DNA damage, by regulating splicing of transcripts like p21, impacting cell cycle control and survival. Mutations or dysregulation of DHX8 disrupt splicing and can result in defects in development, hematopoiesis, and cell cycle control. While DHX8 is not a drug target, it is a crucial enzyme for RNA processing and cellular response to genotoxic stress.
- Other names
- DDX8HRH1PRP22PRPF22Dhr2RNA helicase HRH1DEAH (Asp-Glu-Ala-His) box polypeptide 8DEAH box protein 8
02
Biological functions
Pre-mRNA splicingmRNA release from spliceosomesRegulation of gene expression (via splicing)ATP bindingRNA binding and unwindingRegulation of cell cycle and survival under stress (by modulating splicing of key transcripts like p21)
03
Disease associations
Cancer (regulation of splicing, cell cycle, and apoptosis; mutations linked to hematopoietic defects)Human immunodeficiency virus type 1 (HIV-1) replication (may be required)Cell division abnormalities (model organisms)Congenital anomalies of the kidney and urinary tract (CAKUT, rare association)Other (general RNA processing disorders)
04
Safety considerations
Not applicable for existing therapeutics, as DHX8 is not a clinical target. However, its central role in splicing suggests that genetic or pharmacological inhibition may cause severe defects in RNA processing, cell cycle arrest, or apoptosisPotential for hematopoietic and cell division defects if dysregulated
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