Rewriting the textbook on gene regulation: Its the big picture that counts: UC San Diego researchers rethink the central dogma of molecular biology

A fundamental principle of molecular biology governs how proteins are made within the cell, which happens in two stages called transcription and translation. During transcription, information stored in DNA is copied into messenger RNA (mRNA). Then during translation, the ribosomes assemble proteins one amino acid at a time based on the instruction specified on the mRNA.

The understanding of this process is so fundamental that the mere direction of the information flow from DNA to mRNA to protein is called the “central dogma” of molecular biology, a term coined by Nobel laureate Francis Crick. Since the advent of systems biology 20 years ago, researchers have been trying to establish how cells regulate transcription and translation processes based on gene expression data — which mRNAs and proteins are made under what conditions.

Deciphering how cells regulate these activities would provide insight into how they process environmental information to modulate their behavior. It would also allow scientists to formulate strategies for the precise manipulation of protein levels — a critical step in synthetic biology, which seeks to solve problems in medicine, manufacturing and agriculture through the redesign and re-engineering of genes and their interactions.

For the first time, researchers at the University of California San Diego have shown that changes in gene expression for the model bacterium E. coli happen almost entirely during the transcription stage while the cells are growing. The researchers have provided a simple quantitative formula linking regulatory control to mRNA and protein levels. The results and formula were published in a recent issue of Science.

“Ultimately what we provide is a quantitative relationship that scientists can use to interpret how pathogenic bacteria evade antibiotic treatment and host immunity,” stated Terry Hwa, UC San Diego Distinguished Professor of Physics and Biological Sciences, and principal investigator for the project. “In the synthetic biology context, it will allow bacteria to be redesigned and rewired for uses such as detecting and cleaning up toxic waste, or being sent into the body to kill cancer cells.”

The central dogma of molecular biology is linear, moving from DNA to mRNA to protein. It’s straightforward on an individual-gene level: turn on a gene, make mRNA, create proteins from the mRNA. Often, biologists think of gene regulation in such a linear fashion because they design experiments that change only a single gene or the few genes specific to their studies without drastically affecting the entire cell system.

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