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  • Wypijewska Del Nogal, Anna Wiktoria,1982Chalmers tekniska högskola,Chalmers University of Technology (author)

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

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-08-20
  • MDPI AG,2021
  • electronicrdacarrier

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  • LIBRIS-ID:oai:research.chalmers.se:fb16d2c8-136d-4f98-b4e4-8e3931fe2d49
  • https://research.chalmers.se/publication/525731URI
  • https://doi.org/10.3390/ijms22169008DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • 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.

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  • Sundar Rajan, Vinoth,1987Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)edal (author)
  • Westerlund, Fredrik,1978Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)fredrikw (author)
  • Wilhelmsson, Marcus,1974Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)mawi (author)
  • Chalmers tekniska högskola (creator_code:org_t)

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  • In:International Journal of Molecular Sciences: MDPI AG22:161661-65961422-0067

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Wypijewska Del Nogal, Anna Wiktoria,1982
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