DHX30 Coordinates Cytoplasmic Translation and Mitochondrial Function Contributing to Cancer Cell Survival

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• DHX30 (DEAD-box helicase 30) has been linked to mRNA translation control in p53-dependent apoptosis.
• This study investigates a broader role for DHX30 in integrating cytoplasmic and mitochondrial functions.

Purpose of the Study:

• To elucidate the general function of DHX30 in cellular homeostasis.
• To determine DHX30's role in coordinating translation, proliferation, and mitochondrial metabolism.
• To identify DHX30 targets and explore its prognostic value in cancer.

Main Methods:

• Depletion of DHX30 isoforms in HCT116, U2OS, and MCF7 cell lines.
• Analysis of polysome-associated mRNAs and translational efficiency.
• Isoform-specific silencing experiments.
• RNA immunoprecipitation (RIP), enhanced CLIP (eCLIP), and gene expression analysis.

Main Results:

• DHX30 depletion alters mRNA translation, boosting cytoplasmic ribosomal protein mRNA translation while decreasing mitoribosome mRNA translation.
• Global translation increases, but proliferation and mitochondrial energy metabolism decrease upon DHX30 depletion.
• Cytoplasmic DHX30 specifically modulates global translation.
• Fourteen mitoribosome transcripts are identified as potential direct DHX30 targets.

Conclusions:

• DHX30 plays a crucial role in maintaining cell homeostasis by coordinating ribosome biogenesis, global translation, and mitochondrial metabolism.
• DHX30's function is conserved across different cell lines (HCT116, U2OS, MCF7).
• Targeting DHX30 presents a potential therapeutic strategy against cancer by exploiting cellular vulnerabilities.