Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop

LENARČIČ ŽIVKOVIĆ, Martina, J. ROZMAN and J. PLAVEC. Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop. MOLECULES. Orlando, Florida: Academic Press, 2020, vol. 25, No 20, p. 4867-4882. ISSN 1420-3049. Available from: https://dx.doi.org/10.3390/molecules25204867.

Basic information

• Original name: Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop
• Authors: LENARČIČ ŽIVKOVIĆ, Martina (705 Slovenia, guarantor, belonging to the institution), J. ROZMAN and J. PLAVEC.
• Edition: MOLECULES, Orlando, Florida, Academic Press, 2020, 1420-3049.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: Switzerland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.411
• RIV identification code: RIV/00216224:14740/20:00118353
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.3390/molecules25204867
• UT WoS: 000585504400001
• Keywords in English: G-quadruplex; NMR spectroscopy; structure; osteoporosis
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

Bone remodeling is a fine-tuned process principally regulated by a cascade triggered by interaction of receptor activator of NF-kappa B (RANK) and RANK ligand (RANKL). Excessive activity of the RANKL gene leads to increased bone resorption and can influence the incidence of osteoporosis. Although much has been learned about the intracellular signals activated by RANKL/RANK complex, significantly less is known about the molecular mechanisms of regulation of RANKL expression. Here, we report on the structure of an unprecedented DNA G-quadruplex, well-known secondary structure-mediated gene expression regulator, formed by a G-rich sequence found in the regulatory region of a RANKL gene. Solution-state NMR structural study reveals the formation of a three-layered parallel-type G-quadruplex characterized by an unique features, including a G-A bulge. Although a guanine within a G-tract occupies syn glycosidic conformation, bulge-forming residues arrange in a pseudo-loop conformation to facilitate partial 5/6-ring stacking, typical of G-quadruplex structures with parallel G-tracts orientation. Such distinctive structural features protruding from the core of the structure can represent a novel platform for design of highly specific ligands with anti-osteoporotic function. Additionally, our study suggests that the expression of RANKL gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).