Regulation of Gene-Expression by Mechanical Force, RNA structure, Optical Tweezers

Biological Physics and Biology One Molecule at a Time

Optical tweezers are ideally suited for probing the effects of force upon biological processes. I have previously pioneered the so-called optical force clamp, a feedback-controlled optical tweezers, which maintains a constant force upon a single moving motor protein (Visscher et al., Nature 400,  184-189). While at the University of Arizona our research has focused on the role of mechanical force in the regulation of gene-expression. We not only investigate how tension in DNA controls initiation of transcription by T7 RNA polymerases, but also how it affects the translocation of ribosomes along mRNA, and how force unfolds downstream mRNA structures known to cause translational recoding (-1 frameshifting, -1 FS).

The mechanical unfolding of the HIV-1 RNA hairpin known to trigger -1 FS is observed at a force of ~15 pN by  stretching single molecules with optical tweezers. Analysis of the force vs. extension data indicates that only the  upper stem unfolds and may give rise to -1 FS.