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bioRxiv · 10.1101/222901

Cytoplasmic import and processing of mRNA amplify transcriptional bursts accounting for the majority of cellular noise

Hansen, M. M. K.·Desai, R. V.·Simpson, M. L.·Weinberger, L. S.
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Abstract

Transcription is an episodic process characterized by probabilistic bursts; but how these bursts are modulated by cellular physiology remains unclear and has implications for how selection may act on these fluctuations. Using simulations and single-molecule RNA counting, we examined how cellular processes influence cell-to-cell variability (noise). The results show that RNA noise is amplified in the cytoplasm compared to the nucleus in ~85% of genes across diverse promoters, genomic loci, and cell types (human and mouse). Surprisingly, measurements show further amplification of RNA noise in the cytoplasm, fitting a model of biphasic mRNA conversion between translation- and degradation-competent states. The multi-state translation-degradation of mRNA also causes substantial noise amplification in protein levels, ultimately accounting for ~74% of intrinsic protein variability in cell populations. Overall, the results demonstrate how transcriptional bursts are intrinsically amplified by mRNA processing and indicate mechanisms through which noise could act as a substrate for evolutionary selection.

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Hansen, M. M. K., Desai, R. V., Simpson, M. L., Weinberger, L. S.. 2017-11-21. Cytoplasmic import and processing of mRNA amplify transcriptional bursts accounting for the majority of cellular noise. https://doi.org/10.1101/222901

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