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 Jjournal_title
Biophysical journalauthors
Kim S,Jacobs-Wagner Cdoi
10.1016/j.bpj.2018.02.010subject
Has Abstractpub_date
2018-04-10 00:00:00pages
1718-1729issue
7eissn
0006-3495issn
1542-0086pii
S0006-3495(18)30213-3journal_volume
114pub_type
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