期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms21030767
关键词
RNA G-quadruplex; pre-miRNA-1229; Alzheimer's disease; rs2291418
资金
- N.I.H [9 R15 GM127307-04]
- NSF/S-STEM [DUE-1259941]
- NSF/MRI [CHE-1726824]
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 beta-amyloid (A beta) proteins. An assortment of proteins is responsible for the processing and trafficking of A beta, 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.
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