Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell. 2017 Sep 7;67(5):826-836.e5. doi: 10.1016/j.molcel.2017.07.010. Epub 2017 Aug 3.

Heterogeneity of Stop Codon Readthrough in Single Bacterial Cells and Implications for Population Fitness.

Author information

1
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
2
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
3
Department of Cellular & Molecular Physiology, Yale University, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
4
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA.
5
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA.
6
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address: jiqiang.ling@uth.tmc.edu.

Abstract

Gene expression noise (heterogeneity) leads to phenotypic diversity among isogenic individual cells. Our current understanding of gene expression noise is mostly limited to transcription, as separating translational noise from transcriptional noise has been challenging. It also remains unclear how translational heterogeneity originates. Using a transcription-normalized reporter system, we discovered that stop codon readthrough is heterogeneous among single cells, and individual cells with higher UGA readthrough grow faster from stationary phase. Our work also revealed that individual cells with lower protein synthesis levels exhibited higher UGA readthrough, which was confirmed with ribosome-targeting antibiotics (e.g., chloramphenicol). Further experiments and mathematical modeling suggest that varied competition between ternary complexes and release factors perturbs the UGA readthrough level. Our results indicate that fluctuations in the concentrations of translational components lead to UGA readthrough heterogeneity among single cells, which enhances phenotypic diversity of the genetically identical population and facilitates its adaptation to changing environments.

KEYWORDS:

bet-hedging; release factor; ribosome; stop codon; translational fidelity

PMID:
28781237
PMCID:
PMC5591071
[Available on 2018-09-07]
DOI:
10.1016/j.molcel.2017.07.010
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center