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Article

Characterization of a G-Quadruplex Structure in Pre-miRNA-1229 and in Its Alzheimer’s Disease-Associated Variant rs2291418: Implications for miRNA-1229 Maturation

Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, USA
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 767; https://doi.org/10.3390/ijms21030767
Received: 23 December 2019 / Revised: 17 January 2020 / Accepted: 20 January 2020 / Published: 24 January 2020
(This article belongs to the Special Issue RNA Regulatory Networks)
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. View Full-Text
Keywords: RNA G-quadruplex; pre-miRNA-1229; Alzheimer’s disease; rs2291418 RNA G-quadruplex; pre-miRNA-1229; Alzheimer’s disease; rs2291418
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MDPI and ACS Style

Imperatore, J.A.; Then, M.L.; McDougal, K.B.; Mihailescu, M.R. Characterization of a G-Quadruplex Structure in Pre-miRNA-1229 and in Its Alzheimer’s Disease-Associated Variant rs2291418: Implications for miRNA-1229 Maturation. Int. J. Mol. Sci. 2020, 21, 767. https://doi.org/10.3390/ijms21030767

AMA Style

Imperatore JA, Then ML, McDougal KB, Mihailescu MR. Characterization of a G-Quadruplex Structure in Pre-miRNA-1229 and in Its Alzheimer’s Disease-Associated Variant rs2291418: Implications for miRNA-1229 Maturation. International Journal of Molecular Sciences. 2020; 21(3):767. https://doi.org/10.3390/ijms21030767

Chicago/Turabian Style

Imperatore, Joshua A., McKenna L. Then, Keefe B. McDougal, and Mihaela R. Mihailescu 2020. "Characterization of a G-Quadruplex Structure in Pre-miRNA-1229 and in Its Alzheimer’s Disease-Associated Variant rs2291418: Implications for miRNA-1229 Maturation" International Journal of Molecular Sciences 21, no. 3: 767. https://doi.org/10.3390/ijms21030767

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