Characterizing rate limiting steps in transcription from RNA production times in live cells

Antti Häkkinen, Andre S. Ribeiro

    Research output: Contribution to journalArticleScientificpeer-review

    11 Citations (Scopus)


    Motivation: Single-molecule measurements of live Escherichia coli transcription dynamics suggest that this process ranges from sub- to super-Poissonian, depending on the conditions and on the promoter. For its accurate quantification, we propose a model that accommodates all these settings, and statistical methods to estimate the model parameters and to select the relevant components. Results: The new methodology has improved accuracy and avoids overestimating the transcription rate due to finite measurement time, by exploiting unobserved data and by accounting for the effects of discrete sampling. First, we use Monte Carlo simulations of models based on measurements to show that the methods are reliable and offer substantial improvements over previous methods. Next, we apply the methods on measurements of transcription intervals of different promoters in live E. coli, and show that they produce significantly different results, both in low- and high-noise settings, and that, in the latter case, they even lead to qualitatively different results. Finally, we demonstrate that the methods can be generalized for other similar purposes, such as for estimating gene activation kinetics. In this case, the new methods allow quantifying the inducer uptake dynamics as opposed to just comparing them between cases, which was not previously possible. We expect this new methodology to be a valuable tool for functional analysis of cellular processes using single-molecule or single-event microscopy measurements in live cells.

    Original languageEnglish
    Pages (from-to)1346-1352
    Number of pages7
    Issue number9
    Publication statusPublished - 1 May 2016
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 3

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Computational Theory and Mathematics
    • Computer Science Applications
    • Computational Mathematics
    • Statistics and Probability


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