Summary information and primary citation
- PDB-id
-
8bm6;
SNAP-derived features in text and
JSON formats
- Class
- DNA
- Method
- NMR
- Summary
- Hairpin adopted by oligonucleotide a36 found in the
promoter of auts2 gene
- Reference
-
Novotny A, Plavec J, Kocman V (2023): "Structural
polymorphism driven by a register shift in a CGAG-rich
region found in the promoter of the neurodevelopmental
regulator AUTS2 gene." Nucleic Acids Res.,
51, 2602-2613. doi: 10.1093/nar/gkad117.
- Abstract
- The AUTS2 gene has been shown to influence brain
development by controlling the number of neurons, promoting
the growth of axons and dendrites and regulating neuronal
migration. The expression of two isoforms of AUTS2 protein
is precisely regulated and misregulation of their
expression has been correlated with neurodevelopmental
delay and autism spectrum disorder. A CGAG-rich region,
which includes a putative protein binding site (PPBS),
d(AGCGAAAGCACGAA), was found in the promoter region of
AUTS2 gene. We show that oligonucleotides from this region
adopt thermally stable non-canonical hairpin structures
stabilized by G:C and sheared G:A base pairs arranged in a
repeating structural motif we termed CGAG block. These
motifs are formed consecutively, in a way that exploits a
shift in register throughout the whole CGAG repeat to
maximize the number of consecutive G:C and G:A base pairs.
The differences in CGAG repeat shifting affect the
structure of the loop region, where PPBS residues are
predominantly located, specifically the loop length, types
of base pairs and the pattern of base-base stacking.
Finally, we propose a previously unexplored mechanism, by
which different folds in the CGAG-rich region could cause a
switch in expression between the full-length and C-terminal
isoforms of AUTS2.
