Structural polymorphism driven by a register shift in a CGAG-rich region found in the promoter of the neurodevelopmental regulator AUTS2 gene

Novotný, Aleš (avtor), Plavec, Janez (avtor), Kocman, Vojč (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: chemical biology, nucleic acid chemistry, brain development, neurons, proteins, AUTS2
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 2602–2613
• Številčenje: Vol. 51, iss. 6
• PID: 20.500.12556/RUL-152402
• UDK: 577
• ISSN pri članku: 1362-4962
• DOI: 10.1093/nar/gkad117
• COBISS.SI-ID: 145972995
• Datum objave v RUL: 23.11.2023

Gradivo je del revije

• Naslov: Nucleic acids research (Online)
• Skrajšan naslov: Nucleic acids res. online
• Založnik: Oxford University Press, Nucleic Acids Research
• ISSN: 1362-4962
• COBISS.SI-ID: 2172954

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, razvoj možganov, nevroni, proteini, AUTS2