DNMT1 inhibition by pUG-fold quadruplex RNA

DNMT1 binds with high affinity to pUG-fold RNA. (A) Schematic of a pUG-fold. G and U residues are labeled in green and cyan, respectively. The phosphate backbone is highlighted in gray, and coordinated K⁺ ions are indicated by purple spheres. PDB: 7MKT. (B) Native gel of indicated RNAs with either 100 mM KCl or LiCl included in the folding buffer, the gel running buffer, and the gel itself. (A)₄₀ was used as a marker for an unstructured single-stranded RNA (dashed line). Longer exposure of (AC)₂₀ and (AC)₃₀ staining is shown to the right, due to the low staining of AC sequences by SybrGold. (C) Circular dichroism spectra of (GU)₂₀ in 100 mM KCl (blue) and LiCl (red). (D) Binding curves of (GU)₂₀ bound to DNMT1 in 100 mM KCl (blue) and LiCl (red). (E) Binding curves of (GU)₁₂ and (GU)₁₁ bound to DNMT1 in 100 mM KCl (blue and light purple, respectively) and LiCl (red and orange, respectively). In D and E, points represent mean values and error bars represent SD for n = 3 replicates.