Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study

Area of Science:

• Genomics
• Structural Biology
• Bioinformatics

Background:

• Duplex stem-loops and G-quadruplexes are crucial in biological processes.
• Overlapping sequences can form quadruplex-duplex hybrids (QDH) with unique properties.

Purpose of the Study:

• To conduct a genomic and structural investigation of stem-loop containing quadruplex sequences (SLQS) in the human genome.
• To explore the formation and biological relevance of QDH.

Main Methods:

• Genome-wide survey of SLQS with a maximum loop length of 20 nt.
• In vitro structural verification using nuclear magnetic resonance (NMR) spectroscopy.
• Analysis of SLQS distribution in genic regions, association with gene expression, and mapping to biological hotspots.

Main Results:

• Identified 80,307 SLQS within 60,172 clusters, potentially covering half of all SLQS in the genome.
• Found 48,508 SLQS in genic/promoter regions, with abundant clusters linked to brain tissues.
• Confirmed in vitro QDH formation and elucidated folding topologies, demonstrating sequence-dependent structural variations.

Conclusions:

• Predicted SLQS provide insights into the potential role of QDH in diverse (patho)biological processes.
• SLQS may function as novel regulatory signals, influenced by sequence variations at mutation loci.
• The findings support the biological involvement of SLQS and their potential as therapeutic targets.