Rate-limiting steps in transcription dictate sensitivity to variability in cellular components

Jarno Mäkelä, Vinodh Kandavalli, Andre S. Ribeiro

    Research output: Contribution to journalArticleScientificpeer-review

    10 Citations (Scopus)
    22 Downloads (Pure)

    Abstract

    Cell-to-cell variability in cellular components generates cell-to-cell diversity in RNA and protein production dynamics. As these components are inherited, this should also cause lineage-to-lineage variability in these dynamics. We conjectured that these effects on transcription are promoter initiation kinetics dependent. To test this, first we used stochastic models to predict that variability in the numbers of molecules involved in upstream processes, such as the intake of inducers from the environment, acts only as a transient source of variability in RNA production numbers, while variability in the numbers of a molecular species controlling transcription of an active promoter acts as a constant source. Next, from single-cell, single-RNA level time-lapse microscopy of independent lineages of Escherichia coli cells, we demonstrate the existence of lineage-to-lineage variability in gene activation times and mean RNA production rates, and that these variabilities differ between promoters and inducers used. Finally, we provide evidence that this can be explained by differences in the kinetics of the rate-limiting steps in transcription between promoters and induction schemes. We conclude that cell-to-cell and consequent lineage-to-lineage variability in RNA and protein numbers are both promoter sequence-dependent and subject to regulation.

    Original languageEnglish
    Article number10588
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2017
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 2

    ASJC Scopus subject areas

    • General

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