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.
