Gene expression is mediated by a central dogma from DNA (gene) to RNA and protein.
Fig. 1. Transcription occurs on genes that have only one or two copies in the cell. Many genes also switch probabilistically between an ON state, in which they are continuously transcribed, and an OFF state, in which they are rarely transcribed. This phenomenon is called the transfer bursting.
The dynamics of the transcriptional bursting can be described by the burst frequency, which represents the proportion of the ON state of the promoter, and the burst size, which represents the average number of transcribed mRNA in a single ON state. If the rate of RNA degradation is also known, the average number of RNA molecules in a cell and the magnitude of the cell-to-cell heterogeneity in RNA expression can be estimated (See below). If the rate of RNA degradation and the average number of mRNA molecules are the same, genes with a low burst frequency and a large burst size have a greater heterogeneity in gene expression than the opposite.
Fig.2. The induction of cell-to-cell heterogeneity in gene expression by transcriptional bursting. (A) Relationship between burst size, burst frequency, intracellular average RNA molecule number, intercellular heterogeneity in gene expression, when RNA degradation rate is constant. The dotted line indicates that the average number of RNA molecules in the cell is the same, and the color of the dotted line indicates the difference in the average number of RNA molecules in the cell. (B) The transcriptional bursting also induces a heterogeneity in gene expression levels among alleles. (C) Intrinsic noise can be estimated from the expression level distribution of each allele at the single cell level. One dot indicates the number of mRNAs from each allele in a cell.
In other words, the transcriptional bursting can be a factor that generates the cell-to-cell heterogeneity in gene expression levels. Transcriptional bursting also induces gene expression heterogeneity among alleles in the same cell (Fig. 2B). Therefore, the gene expression noise induced by transcriptional bursting is classified as intrinsic noise that originates noise inside the cell. Other factors are called extrinsic noise. Intrinsic and extrinsic noise can be estimated from the distribution of expression levels between alleles (Fig. 2C). Although it has been known that burst size, burst frequency, and intrinsic noise vary greatly depending on genes, the molecular mechanisms by which they are controlled have not been clarified.