Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies

Science
Nico BattichAlexander van Oudenaarden

Abstract

The regulation of messenger RNA levels in mammalian cells can be achieved by the modulation of synthesis and degradation rates. Metabolic RNA-labeling experiments in bulk have quantified these rates using relatively homogeneous cell populations. However, to determine these rates during complex dynamical processes, for instance during cellular differentiation, single-cell resolution is required. Therefore, we developed a method that simultaneously quantifies metabolically labeled and preexisting unlabeled transcripts in thousands of individual cells. We determined synthesis and degradation rates during the cell cycle and during differentiation of intestinal stem cells, revealing major regulatory strategies. These strategies have distinct consequences for controlling the dynamic range and precision of gene expression. These findings advance our understanding of how individual cells in heterogeneous populations shape their gene expression dynamics.

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Citations

Jul 8, 2020·Journal of the Royal Society, Interface·Ruben Perez-CarrascoRamon Grima
May 27, 2020·Combinatorial Chemistry & High Throughput Screening·Guohua Huang
Oct 8, 2020·Chemical Communications : Chem Comm·Jerrin Thomas George, Seergazhi G Srivatsan
Dec 22, 2020·Briefings in Bioinformatics·Mattia FurlanMattia Pelizzola
May 11, 2020·Cell Stem Cell·Kara L McKinleyOphir D Klein
Jun 9, 2021·Nature Communications·Karoline HollerJan Philipp Junker
Aug 27, 2021·Molecular Systems Biology·Volker BergenFabian J Theis

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