Complex conformational dynamics of the heart failure‐associated pre‐mirna‐377 hairpin revealed by single‐molecule optical tweezers
Journal article, 2021

pre‐miRNA‐377 is a hairpin‐shaped regulatory RNA associated with heart failure. Here, we use single‐molecule optical tweezers to unzip pre‐miRNA‐377 and study its stability and dy-namics. We show that magnesium ions have a strong stabilizing effect, and that sodium ions stabi-lize the hairpin more than potassium ions. The hairpin unfolds in a single step, regardless of buffer composition. Interestingly, hairpin folding occurs either in a single step (type 1) or through the formation of intermediates, in multiple steps (type 2) or gradually (type 3). Type 3 occurs only in the presence of both sodium and magnesium, while type 1 and 2 take place in all buffers, with type 1 being the most prevalent. By reducing the size of the native hairpin loop from fourteen to four nu-cleotides, we demonstrate that the folding heterogeneity originates from the large size of the hairpin loop. Further, while efficient pre‐miRNA‐377 binders are lacking, we demonstrate that the recently developed C2 ligand displays bimodal activity: it enhances the mechanical stability of the pre-miRNA‐377 hairpin and perturbs its folding. The knowledge regarding pre‐miRNA stability and dynamics that we provide is important in understanding its regulatory function and how it can be modulated to achieve a therapeutic effect, e.g., in heart failure treatment.

RNA folding het-erogeneity


RNA‐ligand interaction

RNA dynamics

Optical tweezers



Single‐molecule force spectroscopy

Heart failure


Anna Wiktoria Wypijewska Del Nogal

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Vinoth Sundar Rajan

Chalmers, Biology and Biological Engineering, Chemical Biology

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Marcus Wilhelmsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

International Journal of Molecular Sciences

16616596 (ISSN) 14220067 (eISSN)

Vol. 22 16 9008

Biosensing of miRNA and detection of its drug-interactions

Swedish Foundation for Strategic Research (SSF) (IS14-0041), 2015-01-01 -- 2020-12-31.

Subject Categories

Biochemistry and Molecular Biology

Materials Chemistry




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