In:
International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 3 ( 2020-01-24), p. 767-
Abstract:
Alzheimer’s disease (AD), the most common age-related neurodegenerative disease, is associated with various forms of cognitive and functional impairment that worsen with disease progression. AD is typically characterized as a protein misfolding disease, in which abnormal plaques form due to accumulation of tau and β-amyloid (Aβ) proteins. An assortment of proteins is responsible for the processing and trafficking of Aβ, including sortilin-related receptor 1 (SORL1). Recently, a genome-wide association study of microRNA-related variants found that a single nucleotide polymorphism (SNP) rs2291418 within premature microRNA-1229 (pre-miRNA-1229) is significantly associated with AD. Moreover, the levels of the mature miRNA-1229-3p, which has been shown to regulate the SORL1 translation, are increased in the rs2291418 pre-miRNA-1229 variant. In this study we used various biophysical techniques to show that pre-miRNA-1229 forms a G-quadruplex secondary structure that coexists in equilibrium with the canonical hairpin structure, potentially controlling the production of the mature miR-1229-3p, and furthermore, that the AD-associated SNP rs2291418 pre-miR-1229 changes the equilibrium between these structures. Thus, the G-quadruplex structure we identified within pre-miRNA-1229 could potentially act as a novel therapeutic target in AD.
Type of Medium:
Online Resource
ISSN:
1422-0067
DOI:
10.3390/ijms21030767
Language:
English
Publisher:
MDPI AG
Publication Date:
2020
detail.hit.zdb_id:
2019364-6
SSG:
12
