Charge transport in individual short single-stranded RNA molecules

Charge transport in biomolecules is crucial for many biological and technological applications, including biomolecular electronics devices and biosensors. RNA has become the focus of research because of its importance in biomedicine, but its charge transport properties are poorly understood. Here, we use the Scanning Tunneling Microscopy-assisted molecular break junction method to measure, for the first time, the electrical conductance of 5-base and 10-base single-stranded (ss) RNA sequences. These ssRNAs show single-molecule conductance values around 0.001 G0 (G0 = 2e2/h), while equivalent ssDNAs result in featureless conductance histograms. Circular dichroism (CD) spectra and MD simulations reveal the existence of extended ssRNA conformations versus folded ssDNA conformations, consistent with their different electrical behaviors. Computational molecular modeling and Machine Learning-assisted interpretation of CD data helped us to disentangle the structural and electronic factors underlying CT, thus explaining the observed electrical behavior differences. RNA with a measurable conductance corresponds to sequences with overall extended base-stacking stabilized conformations characterized by lower HOMO energy levels delocalized over a base-stacking mediating CT. In contrast, DNA and a control RNA sequence tend to form closed structures and thus are incapable of efficient CT.