Abstract
Recent evidence indicates that transcriptional bursts are intrinsically
amplified by messenger RNA cytoplasmic processing to generate large
stochastic fluctuations in protein levels. These fluctuations can be
exploited by cells to enable probabilistic bet-hedging decisions. But
large fluctuations in gene expression can also destabilize cell-fate
commitment. Thus, it is unclear if cells temporally switch from high to
low noise, and what mechanisms enable this switch. Here, the discovery
of a post-transcriptional mechanism that attenuates noise in HIV is
reviewed. Early in its life cycle, HIV amplifies transcriptional
fluctuations to probabilistically select alternate fates, whereas at
late times, HIV utilizes a post-transcriptional feedback mechanism to
commit to a specific fate. Reanalyzing various reported
post-transcriptional negative feedback architectures reveals that they
attenuate noise more efficiently than classic transcriptional
autorepression, leading to the derivation of an assay to detect
post-transcriptional motifs. It is hypothesized that coupling
transcriptional and post-transcriptional autoregulation enables
efficient temporal noise control to benefit developmental bet-hedging
decisions.
