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Abstract
Molecular noise refers to fluctuations of biological signals that facilitate phenotypic heterogeneity in a population. While endogenous mechanisms exist to limit genetic noise in biological systems, such restrictions are sometimes removed to propel phenotypic variability as an adaptive strategy. Herein, we review evidence for the potential role of β-catenin in restricting gene expression noise by transcriptional and post-transcriptional mechanisms. We discuss mechanisms that restrict intrinsic noise subsequent to nuclear mobilization of β-catenin. Nuclear β-catenin promotes initiation of transcription but buffers against the resultant noise by restraining transcription elongation. Acceleration of cell cycle, mediated via Wnt/β-catenin downstream signals, further diminishes intrinsic noise by curtailing the efficiency of protein synthesis. Extrinsic noise, on the other hand, is restricted by β-catenin–mediated regulation of major cellular stress pathways.
Highlights
In biological systems, noise can be defined as variability in transmission of a signal between two sources
It may be concluded that network-level wiring of β-catenin to other signaling cascades moderates its activity and provides an excess capacity that could be unleashed to repress gene expression noise with higher efficiency
It may be concluded that evolution of β-catenin, in addition to its documented role in organization of cytoskeleton, provided metazoan life forms with a capacity to modulate gene expression noise
Summary
Noise can be defined as variability in transmission of a signal between two sources. Nuclear localization of β-catenin and the resultant trans-activation are two parallel events that synergistically regulate intrinsic and extrinsic noises in gene expression. Altered processivity of RNAP-II and the resultant inefficiency of transcription reduces transcriptional noise by diminishing the global availability of transcripts and buffering the transcribed mRNAs against promoter-driven fluctuations during transcription initiation (Ko, 1991; Raser and O’Shea, 2004; 2005).
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