mRNA-protein assembly reduces fluctuations in a system with bursty transcription

TL;DR

This study investigates how mRNA-protein assemblies can buffer transcription noise, showing that even small assemblies of a few mRNAs effectively regulate transcript fluctuations and facilitate controlled gene expression.

Contribution

The paper provides a quantitative analysis of noise suppression by mRNA-protein assemblies, highlighting their role in reducing transcriptional variability even with minimal assembly sizes.

Findings

Assemblies of just a few mRNAs can significantly suppress fluctuations.

Noise buffering is most effective when mRNA production is near the assembly threshold.

The mechanism facilitates regulated transcription by reducing burst-induced variability.

Abstract

mRNA-protein assemblies play a fundamental role in forming membraneless compartments within cells, whose functions may include activating, inhibiting, and localizing reactions. Recruitment of proteins into droplets can diminish cell to cell variability in protein abundance. However, the extent to which mRNA-protein assemblies may also buffer noise arising from transcription is not understood. Complicating study of this question is that models of kinetics typically treat this as a phase separation process, when mRNA-protein assemblies can contain as few as 2 mRNA transcripts, far below the thermodynamic thresholds for phase separation. Here, through stochastic simulations and asymptotic analysis, we quantify noise suppression by mRNA-protein assemblies as a function of gene expression kinetic parameters, and show that assemblies formed from just a handful of mRNAs effectively regulate transcript abundances and suppress fluctuations. We place particular emphasis on how this mechanism can facilitate regulated transcription by reducing noise even in the context of infrequent bursts of transcription. We investigate two biologically relevant models in which mRNA assembly acts to either "buffer" noise by storing mRNA in inert droplets, or "filter" assembled mRNAs by accelerating their decay, and quantify expression noise as a function of kinetic parameters. In either case, the most controlled expression occurs when bursts produce mRNAs close to the assembly threshold, which we find to be broadly consistent with observations of an RNP-droplet forming cyclin in multinucleate \textit{Ashbya gossypii} cells.