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Bursting translation on single mRNAs in live cells.
Livingston, Nathan M; Kwon, Jiwoong; Valera, Oliver; Saba, James A; Sinha, Niladri K; Reddy, Pranav; Nelson, Blake; Wolfe, Clara; Ha, Taekjip; Green, Rachel; Liu, Jian; Wu, Bin.
Afiliação
  • Livingston NM; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kwon J; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Valera O; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Saba JA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Sinha NK; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Reddy P; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nelson B; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Wolfe C; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Ha T; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Green R; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Liu J; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jliu187@jhmi.edu.
  • Wu B; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of
Mol Cell ; 83(13): 2276-2289.e11, 2023 Jul 06.
Article em En | MEDLINE | ID: mdl-37329884
ABSTRACT
Stochasticity has emerged as a mechanism of gene regulation. Much of this so-called "noise" has been attributed to bursting transcription. Although bursting transcription has been studied extensively, the role of stochasticity in translation has not been fully investigated due to the lack of enabling imaging technology. In this study, we developed techniques to track single mRNAs and their translation in live cells for hours, allowing the measurement of previously uncharacterized translation dynamics. We applied genetic and pharmacological perturbations to control translation kinetics and found that, like transcription, translation is not a constitutive process but instead cycles between inactive and active states, or "bursts." However, unlike transcription, which is largely frequency-modulated, complex structures in the 5'-untranslated region alter burst amplitudes. Bursting frequency can be controlled through cap-proximal sequences and trans-acting factors such as eIF4F. We coupled single-molecule imaging with stochastic modeling to quantitatively determine the kinetic parameters of translational bursting.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica Idioma: En Ano de publicação: 2023 Tipo de documento: Article