When It Comes to Genetic Code, Optimum Isn't Always Best
News Feb 22, 2013
A team of researchers including a Texas A&M University molecular biologist has shown that concept -- that the speed of creation affects performance -- applies to how a protein they studied impacts an organism's circadian clock function. This discovery provides new insights into the significance of the genetic code for controlling the rates at which critically important proteins are synthesized, and could lead to better understanding of cancers and other diseases.
"Living organisms' inner clocks are like Swiss watches with precisely manufactured spring mechanisms," said Matthew Sachs, a professor in the Texas A&M Department of Biology. "For example, if you fast-temper a critical spring, the watch may be unable to keep time, as opposed to slow-tempering it. It's not just about the composition of the components, such as which alloy is used. It's about the manner in which the components are made. Our research says the genetic code is important for determining both composition and fabrication rate for a central component of the circadian clock, and that the fabrication rate also is critical. And that's essentially a discovery."
The research, funded in part by the National Institutes of Health and the Houston-based Welch Foundation, was selected for Advanced Online Publication (AOP) in the prestigious journal Nature.
The team, which is led by Yi Liu, a researcher in the Department of Physiology at the University of Texas Southwestern Medical Center, was perplexed when it found a paradoxical result years ago: that optimizing the use of codons (a sequence of three nucleotides that form a unit of genetic code in a DNA or RNA molecule) specifying an essential biological clock component actually abolished the organism's circadian rhythms.
The group's research indicates that the protein in the fungal genus Neurospora they studied, frequency, performs better when the genetic code specifying it has non-optimal codon usage, as is normally found. However, when the genetic code is deliberately altered so that codon usage is optimized, clock function is lost. The reason for this is that non-optimal codon usage slows translation of the genetic code into protein, allotting the frequency protein the necessary time to achieve its optimal protein structure.
The team's results also demonstrate that genetic codons do more than simply determine the amino acid sequence of a protein as previously thought: They also affect how much protein can be made as well as the functional quality of that protein.
"We found that less is more, in many cases," Liu said.
Because many genetic diseases are the result of improperly functioning proteins, Sachs says knowledge about how proteins are made and why they have impaired functions is critical to understanding almost all diseases.
"Understanding gene expression is crucial for understanding cancer and other diseases, because ultimately many of these processes involve either mutations of genes or altered expression of genes," said Sachs, who was asked by Liu to help on the research because of his translational expertise in Neurospora.
In addition to Liu and Sachs, the paper's authors include Mian Zhou, Jinhu Guo, Joonseok Cha and Michael Chae, all from the Department of Physiology at UT Southwestern Medical Center; She Chen from the National Institute of Biological Sciences in Beijing; and Jose M. Barral from the Departments of Neuroscience and Cell Biology and Biochemistry and Molecular Biology at UT Medical Branch in Galveston.
CRISPR Reveals New Targets for Promising Cancer DrugsNews
Novel screening method identifies new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.READ MORE
Big-Data Analysis Points Toward New Drug Discovery MethodNews
A research team has developed a computational method to systematically probe massive amounts of open-access data to discover new ways to use drugs, including some that have already been approved for other uses.
RNA Molecules Lives Are 10 Times Shorter Than Previously ThoughtNews
A research group at the Biozentrum of the University of Basel has developed a new method to measure the half-life of RNA molecules.READ MORE
Comments | 0 ADD COMMENT
EMBL Course: Next Generation Sequencing: RNA Sequencing Library Preparation
Apr 23 - Apr 27, 2018
EMBO Practical Course: Microbial Metagenomics: A 360º Approach
Apr 23 - Apr 30, 2018
EMBL Course: Next Generation Sequencing: Whole Genome Sequencing Library Preparation
Apr 16 - Apr 20, 2018
EMBO Workshop: Integrating Systems Biology: From Networks to Mechanisms to Models
Apr 15 - Apr 17, 2018