Dynamics of Gene Silencing in a Live Cell: Stochastic Resonance

Abstract

Binding of a specific siRNA to the target mRNA in a live cell (human breast cancer cell, MCF-7) is studied by confocal microscopy. The specific siRNA (labeled with a fluorophore, alexa 488) exhibits much higher intensity of fluorescence in the bound state than in the free (unbound) state. It is observed that repeated unbinding and rebinding of siRNA (to target mRNA) occur before gene silencing. 16 273 on-time periods (residence or dwell time of siRNA in bound form) are detected. They follow a strikingly simple pattern. All of the on-time periods are odd-integral multiples of 5.5 ± 0.05 ms. This is ascribed to stochastic resonance.

Environmental Fluctuations and Stochastic Resonance in Protein Folding

“…It is not known at present whether cells use stochastic resonance to modulate biomolecule function outside the cases of signaling or visual signal enhancement that have been studied . However, our results show that it is a physically plausible process.…”

“…[26, 31] However, our results show that it is a physically plausible process. There is growing evidence that many proteins in the cell, for example certain intrinsically disordered protein (IDPs), can switch conformation based on small perturbations.…”

“…[30] In particular, stochastic resonance plays a role in biochemical reactions, such as cell signaling, where noise due to a small number of signaling molecules can control gene silencing. [31][32] …”

“…Examples include pulsing Belousov‐Zhabotinsky reactions, as well as electron transfer reactions . In particular, stochastic resonance plays a role in biochemical reactions that are part of feedback cycles, such as cell signaling, where noise due to a small number of signaling molecules can control gene silencing …”

Role of Red-Ox Cycle in Structural Oscillations and Solvation Dynamics in the Mitochondria of a Live Cell

“…19−22 Most recently, we have detected stochastic resonance in silencing of a gene in a live cell by short interfering RNA. 23 Single-molecule fluorescence spectroscopy has been employed to investigate structural organization and conformational changes of Kinesin-1 in live cells, 24 nucleotide binding to kinesin motor heads using fluorescent ATP analogue, 25 and dynamics of kinesin motor domain. 26 Surrey and coworkers investigated the dynamics of microtubule plus end-tracking protein using time-resolved microscopy.…”