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Structural basis for nucleolin recognition of MYC promoter G-quadruplex

GSE276539 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/05/05 Platform GPL24676
Summary
The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K+), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery.
Published in
Structural basis for nucleolin recognition of MYC promoter G-quadruplex
Chen L, Dickerhoff J, Zheng KW et al. · Science (New York, N.Y.) 2025 · PMID 40245140 · doi:10.1126/science.adr1752
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Also filed as BioProject PRJNA1156828 and SRA study SRP530704. Searching any of these in the dataset finder brings you back here.

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