Translation initiation events on structured eukaryotic mRNAs generate gene expression noise

Area of Science:

• Molecular Biology
• Systems Biology
• Genetics

Background:

• Gene expression stochasticity, or noise, creates non-genetic cellular individuality.
• This noise influences critical biological processes such as differentiation and stress responses.
• Posttranscriptional contributions to gene expression noise remain under-explored.

Purpose of the Study:

• To investigate posttranscriptional mechanisms contributing to gene expression noise.
• To determine cell-to-cell variations in mRNA and reporter protein abundance in yeast.
• To identify specific mRNA structural elements that generate noise.

Main Methods:

• Insertion of stem-loop and poly(G) motifs into the 5' untranslated region of mRNA in yeast.
• Measurement of cell-to-cell variations in mRNA and reporter protein levels.
• Computational modeling to simulate noise generation mechanisms.

Main Results:

• Stem-loop and poly(G) motifs inhibit translation initiation and generate significant noise.
• The noise-enhancing effect of stem-loops persists even with an upstream open reading frame.
• Findings suggest posttranscriptional noise is linked to structural dynamics of mRNA elements.

Conclusions:

• Posttranscriptional mechanisms, particularly mRNA structural elements, are significant sources of gene expression noise.
• This noise can be attributed to structural dynamics like stem-loop folding/unfolding or G-rich motif interconversions.
• Understanding posttranscriptional noise is crucial for explaining the poor correlation between protein stochasticity and transcriptional bursting.