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.

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What drives large mammalian cell-to-cell mRNA variation here?

Intrinsically random, infrequent gene activation events (transcriptional bursts).

How often do genes switch between active and inactive states?

Infrequently, producing large expression variation in clonal lines.

Are these transitions mainly extrinsic?

No—they are intrinsically random and not due to extrinsic factors.

Which native gene also showed bursty mRNA production?

The gene encoding the large subunit of RNA polymerase II.

What method counted individual mRNA molecules?

Fluorescent probes / FISH to visualize single transcripts.

What quantitative comparison supports burst-like transcription?

Comparing mRNA numbers in cells with vs without active transcription sites.

What do bursts imply for clonal cell lines?

Genetically identical cells can still differ widely in expression.

Do bursts affect only engineered reporters?

No—natural genes also show burst-like synthesis.

What is the paper’s core biological claim?

Stochastic mRNA synthesis from infrequent gene activation creates expression noise.

How do mammalian results contrast with yeast noise studies cited?

Yeast variation was mostly extrinsic; here transitions are intrinsic.

What products of gene expression did they measure?

mRNA—the immediate, fast-decaying products—rather than only protein.