Effects of mRNA Degradation and Site-Specific Transcriptional Pausing on Protein Expression Noise.

Abstract:

:Genetically identical cells exhibit diverse phenotypes even when experiencing the same environment. This phenomenon in part originates from cell-to-cell variability (noise) in protein expression. Although various kinetic schemes of stochastic transcription initiation are known to affect gene expression noise, how posttranscription initiation events contribute to noise at the protein level remains incompletely understood. To address this question, we developed a stochastic simulation-based model of bacterial gene expression that integrates well-known dependencies between transcription initiation, transcription elongation dynamics, mRNA degradation, and translation. We identified realistic conditions under which mRNA lifetime and transcriptional pauses modulate the protein expression noise initially introduced by the promoter architecture. For instance, we found that the short lifetime of bacterial mRNAs facilitates the production of protein bursts. Conversely, RNA polymerase (RNAP) pausing at specific sites during transcription elongation can attenuate protein bursts by fluidizing the RNAP traffic to the point of erasing the effect of a bursty promoter. Pause-prone sites, if located close to the promoter, can also affect noise indirectly by reducing both transcription and translation initiation due to RNAP and ribosome congestion. Our findings highlight how the interplay between transcription initiation, transcription elongation, translation, and mRNA degradation shapes the distribution in protein numbers. They also have implications for our understanding of gene evolution and suggest combinatorial strategies for modulating phenotypic variability by genetic engineering.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Kim S,Jacobs-Wagner C

doi

10.1016/j.bpj.2018.02.010

subject

Has Abstract

pub_date

2018-04-10 00:00:00

pages

1718-1729

issue

7

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(18)30213-3

journal_volume

114

pub_type

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