8BM4

Hairpin adopted by modified oligonucleotide A32_mod found in the promoter of AUTS2 gene.

8BM4 の概要

• エントリーDOI: 10.2210/pdb8bm4/pdb
• 関連するPDBエントリー: 8BM6 8BM7
• NMR情報: BMRB: 34768
• 分子名称: A32_mod (1 entity in total)
• 機能のキーワード: auts2, sheared ga, cgag block, hairpin, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9943.42

構造登録者

Novotny, A. (登録日: 2022-11-10, 公開日: 2023-02-22, 最終更新日: 2024-06-19)

主引用文献

Novotny, A.,Plavec, J.,Kocman, V.
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, 2023

PubMed 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.

PubMed: 36864756
DOI: 10.1093/nar/gkad117

実験手法

SOLUTION NMR