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

G-quadruplexes (G4s) are secondary DNA and RNA structures stabilized by positive cations in a central channel formed by stacked tetrads of Hoogsteen base-paired guanines. G4s form from G-rich sequences across the genome, whose biased distribution in regulatory regions points towards a gene-regulator...

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Published in:International journal of molecular sciences 2024-02, Vol.25 (3), p.1753
Main Authors: Gumina, Joseph M, Richardson, Adam E, Shojiv, Mahmudul Hasan, Chambers, Antonio E, Sandwith, Siara N, Reisinger, Michael A, Karns, Taylor J, Osborne, Tyler L, Alashi, Hasna N, Anderson, Quinn T, Sharlow, Meredith E, Seiler, Dylan C, Rogers, Evan M, Bartosik, Anna R, Smaldino, Melissa A, Vaughn, James P, Wang, Yuh-Hwa, Smaldino, Philip J, Haney, Robert A
Format: Article
Language:English
Subjects:
Binding sites
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - metabolism
DHX36
Enzymes
Epigenetics
Fibroblasts
G-quadruplex
G-Quadruplexes
G4R1
Gene Expression
Genomes
Genomics
helicase
Humans
Jurkat Cells - metabolism
leukemia
Ligands
Neoplasms
Proteins
RHAU
RNA - metabolism
Transcription factors
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Summary:G-quadruplexes (G4s) are secondary DNA and RNA structures stabilized by positive cations in a central channel formed by stacked tetrads of Hoogsteen base-paired guanines. G4s form from G-rich sequences across the genome, whose biased distribution in regulatory regions points towards a gene-regulatory role. G4s can themselves be regulated by helicases, such as DHX36 (aliases: G4R1 and RHAU), which possess the necessary activity to resolve these stable structures. G4s have been shown to both positively and negatively regulate gene expression when stabilized by ligands, or through the loss of helicase activity. Using knockout Jurkat cell lines, we identified widespread, although often subtle, effects on gene expression that are associated with the presence or number of observed G-quadruplexes in promoters or gene regions. Genes that significantly change their expression, particularly those that show a significant increase in RNA abundance under knockout, are associated with a range of cellular functions and processes, including numerous transcription factors and oncogenes, and are linked to several cancers. Our work highlights the direct and indirect role of DHX36 in the transcriptome of T-lymphocyte leukemia cells and the potential for DHX36 dysregulation in cancer.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25031753