Differential Gene Expression following DHX36/G4R1 Knockout Is Associated with G-Quadruplex Content and Cancer

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• G-quadruplexes (G4s) are stable secondary DNA/RNA structures formed by G-rich sequences.
• These structures are found in regulatory genomic regions and can influence gene expression.
• Helicases like DHX36 (G4R1, RHAU) resolve G4s, playing a role in their regulation.

Purpose of the Study:

• To investigate the role of DHX36 in regulating gene expression in the context of G-quadruplex structures.
• To identify genes affected by DHX36 activity or inactivity in T-lymphocyte leukemia cells.

Main Methods:

• Utilized DHX36 knockout Jurkat cell lines.
• Analyzed gene expression changes associated with G-quadruplex presence and DHX36 status.
• Correlated gene expression alterations with genomic locations of G-quadruplexes.

Main Results:

• DHX36 knockout led to widespread, often subtle, changes in gene expression.
• Increased RNA abundance was observed for specific genes upon DHX36 loss.
• Affected genes included transcription factors and oncogenes, with links to various cancers.

Conclusions:

• DHX36 plays a direct and indirect role in regulating the transcriptome of T-lymphocyte leukemia cells.
• Dysregulation of DHX36 may contribute to cancer development.
• G-quadruplexes and their interaction with helicases are critical in gene regulation and disease.