Mechanical pulling through a nanopore can reveal the secondary structure of single RNA molecules

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Abstract
We investigate theoretically the driven translocation of RNA molecules through narrow pores which allow single but not double strands to pass. In particular, we consider the situation where the driving force is exerted mechanically with a device that records force-extension curves (FEC's), e.g. optical tweezers. We argue that such a setup can be used to determine the secondary structure, including pseudoknots, of RNA on a single-molecule level. For an exemplary RNA sequence, the Tetrahymena group I intron, we calculate such FEC's and demonstrate the reconstruction of the secondary structure explicitly. Our calculation of the FEC's is based on the experimentally determined free energy rules for RNA secondary structures and a simplified model for the translocation kinetics, while the reconstruction uses only the FEC's and the RNA nucleotide sequence. We estimate that pulling speeds on the order of 1 $\mu$m/s would be suitable for an experimental implementation of the proposed method.

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