Stochastic mRNA synthesis in mammalian cells

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Genetically identical cells show protein expression variability.
• Understanding the origins of this cellular heterogeneity is crucial.

Purpose of the Study:

• Investigate the origins of molecular variations in mammalian cells.
• Characterize mRNA synthesis dynamics and their impact on gene expression noise.

Main Methods:

• Quantified individual mRNA molecules from a reporter gene in mammalian cells.
• Developed a stochastic model for gene activation/inactivation.
• Analyzed gene expression within genomic loci.

Main Results:

• Massive, cell-to-cell variations in mRNA counts were observed.
• mRNA synthesis occurs in short, intense bursts due to random gene state transitions.
• Burst-like expression affects multiple genes in a genomic locus.
• Bursting is also evident in natural genes and can be buffered by slow protein degradation.

Conclusions:

• Intrinsic randomness in gene activation/inactivation drives significant gene expression noise in mammalian cells.
• Transcription factor levels influence burst size, not frequency.
• Cellular function in the face of such inherent noise remains an open question.