Navigation Links
Penn biologists discover how 'silent' mutations influence protein production

PHILADELPHIA - Biologists at the University of Pennsylvania have revealed a hidden code that determines the expression level of a gene, providing a way to distinguish efficient genes from inefficient ones. The new research, which involved creating hundreds of synthetic green-glowing genes, provides an explanation for how a cell "knows" how much of each protein to make, providing just the right amount of protein to maintain homeostasis yet not too much to cause cell toxicity.

In the study, Penn biologists analyzed how protein levels are governed by synonymous, or silent, mutations within the protein-coding region.

Synonymous mutations do not change the amino-acid sequence of a protein, but they can nevertheless influence the amount of the protein that is produced. The researchers identified the mechanism underlying this regulation: synonymous mutations determine mRNA folding and thereby the eventual protein level. The researchers also identified a class of mutations that did not directly affect protein levels but slowed bacterial growth.

For biologists, these results fundamentally change the understanding of the role of synonymous mutations, which were previously considered evolutionarily neutral. The findings may also improve the design of therapeutic genes. Many drugs, such as insulin, are produced by transgenic cell lines. Using optimized genes will produce larger amounts of therapeutic proteins while keeping the transgenic, carrier cells healthy and fast-growing.

The human genome contains more than 20,000 genes that encode the proteins present in a human body. Some of these proteins are needed in bulk, while for others a tiny amount is sufficient and a large amount would be toxic. The question is how cells "know" how much of each protein to make.

To answer this question, Joshua B. Plotkin, senior author and the Martin Meyerson Assistant Professor in the Department of Biology in Penn's School of Arts and Sciences, and colleagues at Harvard University and the University of Edinburgh engineered a synthetic library of 154 genes that varied randomly at synonymous sites. All the genes encoded the same green fluorescent protein, enabling the researchers to easily study the effects of such mutations on protein levels when expressed in the bacterium Escherichia coli.

The silent mutations changed the amount of fluorescent protein by as much as 250-fold, without changing the properties of the protein. Codon bias, the probability that one codon of three adjacent nucleotides will code for one amino acid over another, was previously thought to be the cause for protein expression variance, but it did not correlate with gene expression in these experiments.

"At first we were stumped," Plotkin said. "How were the silent mutations influencing protein levels? Eventually, we looked at mRNA structure and discovered that this was the underlying mechanism."

The stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. To understand this observation, the researchers simulated the spatial arrangement of the messenger RNA molecule that carries the information from genes to proteins. They found that the inefficient genes produced tightly folded mRNA molecules that could not be accessed by the protein-making machinery. According to their analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.


Contact: Jordan Reese
University of Pennsylvania

Related biology news :

1. UIC biologists use DNA to study migration of threatened whale sharks
2. Penn biologists demonstrate that size matters... in snail shells
3. Two innovative University of Texas at Austin biologists become HHMI Early Career Scientists
4. Plant biologists discover gene that switches on essence of male
5. Cleaning up oil spills can kill more fish than spills themselves, say Queens biologists
6. Biologists solve mystery of black wolves
7. Biologists discover link between CGG repeats in DNA and neurological disorders
8. Biologists learn structure, mechanism of powerful molecular motor in virus
9. Queens University biologists find new environmental threat in North American lakes
10. Biologists discover gene behind plant sex mystery
11. Caltech geobiologists discover unique magnetic death star fossil
Post Your Comments:
Related Image:
Penn biologists discover how 'silent' mutations influence protein production
(Date:6/2/2016)...   The Weather Company , an IBM Business (NYSE: ... capability in which consumers will be able to interact with ... via voice or text and receive relevant information about the ... Marketers have long sought an advertising solution that can create ... relevant and valuable; and can scale across millions of interactions ...
(Date:5/24/2016)... IRVINE, Calif. , May 24, 2016 Ampronix facilitates superior patient care ... LMD3251MT  3D medical LCD display is the latest premium product recently added to ... ... ... Sony 3d Imaging- LCD Medical Display- Ampronix News ...
(Date:5/12/2016)... 2016 , a brand of ... results from the Q1 wave of its quarterly wearables ... consumers, receptivity to a program where they would receive ... insurance company. "We were surprised to see ... Michael LaColla , CEO of Troubadour Research, "primarily because ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... Seattle, WA (PRWEB) , ... June 23, 2016 ... ... technology, announces the release of its second eBook, “Clinical Trials Patient Recruitment and ... patient recruitment and retention in this eBook by providing practical tips, tools, and ...
(Date:6/23/2016)... - FACIT has announced the creation of a ... Propellon Therapeutics Inc. ("Propellon" or "the Company"), to ... of first-in-class WDR5 inhibitors for the treatment of ... an exciting class of therapies, possessing the potential ... patients. Substantial advances have been achieved with the ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute approval ... of microbial tests introduced last year,” stated Bob Salter, Vice President of Regulatory ...
(Date:6/23/2016)... 23, 2016   EpiBiome , a precision microbiome ... in debt financing from Silicon Valley Bank (SVB). The ... to advance its drug development efforts, as well as ... "SVB has been an incredible strategic partner to ... traditional bank would provide," said Dr. Aeron Tynes ...
Breaking Biology Technology: