The translational landscape as regulated by the RNA helicase DDX3
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Continuously renewing the proteome, translation is exquisitelycontrolled by a number of dedicated factors that interact withthe ribosome. The RNA helicase DDX3 belonging to the DEADbox family has emerged as one of the critical regulators of translation,the failure of which is frequently observed in a wide rangeof proliferative, degenerative, and infectious diseases in humans. DDX3 unwinds double-stranded RNA molecules with coupledATP hydrolysis and thereby remodels complex RNA structurespresent in various protein-coding and noncoding RNAs. By interactingwith specific features on messenger RNAs (mRNAs) and18S ribosomal RNA (rRNA), DDX3 facilitates translation, whilerepressing it under certain conditions. We review recent findingsunderlying these properties of DDX3 in diverse modes of translation,such as cap-dependent and cap-independent translationinitiation, usage of upstream open reading frames, and stress-inducedribonucleoprotein granule formation. We further discusshow disease-associated DDX3 variants alter the translation landscapein the cell.
Abstract
Continuously renewing the proteome, translation is exquisitelycontrolled by a number of dedicated factors that interact withthe ribosome. The RNA helicase DDX3 belonging to the DEADbox family has emerged as one of the critical regulators of translation,the failure of which is frequently observed in a wide rangeof proliferative, degenerative, and infectious diseases in humans. DDX3 unwinds double-stranded RNA molecules with coupledATP hydrolysis and thereby remodels complex RNA structurespresent in various protein-coding and noncoding RNAs. By interactingwith specific features on messenger RNAs (mRNAs) and18S ribosomal RNA (rRNA), DDX3 facilitates translation, whilerepressing it under certain conditions. We review recent findingsunderlying these properties of DDX3 in diverse modes of translation,such as cap-dependent and cap-independent translationinitiation, usage of upstream open reading frames, and stress-inducedribonucleoprotein granule formation. We further discusshow disease-associated DDX3 variants alter the translation landscapein the cell.
참고문헌 (100)
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