Why do identical cells make different amounts of mRNA?
Mammalian genes switch rarely between ON and OFF, so intrinsically random transcriptional bursts create large cell-to-cell mRNA differences.
Source
Stochastic mRNA synthesis in mammalian cells
Inspect source passages
Why do identical cells make different amounts of mRNA?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
What drives large mammalian cell-to-cell mRNA variation here?
We have shown that the mRNA levels of both reporter genes and native genes display large cell-to-cell variations in mammalian cells due to intrinsically random, infrequent events of gene activation.
How often do genes switch between active and inactive states?
we show direct evidence that genes transition infrequently between active and inactive states, resulting in large cell-to-cell variations in gene expression in clonal cell lines.
What they did
Used FISH to count individual reporter and native mRNA molecules in clonal mammalian cells and tested whether variation was intrinsic or extrinsic.
What they found
Genes transition infrequently between active and inactive states; bursts are intrinsically random (not mainly extrinsic) and affect whole genomic loci, including RNA polymerase II large-subunit mRNA.
The limits
What it doesn't show
Does not map every mammalian gene’s burst kinetics in vivo tissues, or prove a single molecular switch mechanism for all loci.
Key terms
- Transcriptional bursting
- Episodes of active mRNA production separated by silent periods.
- Intrinsic noise
- Randomness from the gene’s own molecular events.
- Extrinsic noise
- Cell-wide factor differences that co-vary across genes.
- FISH
- Fluorescence in situ hybridization to visualize single mRNA molecules.
- Gene expression noise
- Cell-to-cell variation in expression among genetically identical cells.
Flashcards
0 of 11 answers reviewed
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
Quiz yourself
Main source of mammalian expression noise here?
Common questions
Is the variation mainly extrinsic like in yeast?
No—the authors argue mammalian transitions are intrinsically random.
Do natural genes burst too?
Yes—including Pol II large-subunit mRNA.
How were molecules counted?
Single-molecule FISH with tandem probe-binding sites.
What causes large expression differences?
Infrequent ON/OFF transitions and bursty synthesis.
More on Gene expression