期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 12, 页码 7179-7188出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab531
关键词
-
资金
- National Natural Science Foundation of China
The study systematically characterized the mechanical stability of parallel-stranded G4s with bulges, finding that the positions and lengths of the bulges strongly influence their folding probability and conformations. The research also demonstrated a new strategy for selectively stabilizing the intermediates of bulged G4s to modulate their functions.
A significant number of sequences in the human genome form noncanonical G-quadruplexes (G4s) with bulges or a guanine vacancy. Here, we systematically characterized the mechanical stability of parallel-stranded G4s with a one to seven nucleotides bulge at various positions. Our results show that G4-forming sequences with a bulge form multiple conformations, including fully-folded G4 with high mechanical stability (unfolding forces > 40 pN), partially-folded intermediates (unfolding forces < 40 pN). The folding probability and folded populations strongly depend on the positions and lengths of the bulge. By combining a single-molecule unfolding assay, dimethyl sulfate (DMS) footprinting, and a guanine-peptide conjugate that selectively stabilizes guanine-vacancy-bearing G-quadruplexes (GVBQs), we identified that GVBQs are the major intermediates of G4s with a bulge near the 5' or 3' ends. The existence of multiple structures may induce different regulatory functions in many biological processes. This study also demonstrates a new strategy for selectively stabilizing the intermediates of bulged G4s to modulate their functions.
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