Translation initiation events on structured eukaryotic mRNAs generate gene expression noise

Nucleic Acids Research
Estelle DacheuxJohn E G McCarthy

Abstract

Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem-loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem-loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a ...Continue Reading

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Citations

Jan 19, 2018·Annual Review of Biophysics·Evelina TutucciBin Wu
Jan 22, 2020·PloS One·Alexandra GoetzMadeleine Opitz
May 28, 2019·Frontiers in Genetics·Marylène VandevenneMoreno Galleni
Oct 23, 2020·The FEBS Journal·Tailise Carolina de Souza-GuerreiroJohn McCarthy
Dec 10, 2020·Journal of Developmental Biology·Duncan WotherspoonRyan F L O'Shaughnessy
Jul 17, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·John McCarthy
Jan 26, 2018·ACS Synthetic Biology·Thomas DecoeneMarjan De Mey

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Methods Mentioned

BETA
smFISH
flow cytometry
NMR

Software Mentioned

R
flowViz
COPASI
R script
flowDensity Bioconductor
FACSDiva
smFISH
flowCore

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