Translation, the process of converting a cell's genetic code into proteins, is a complicated process with many opportunities for mistakes - but it needs to work almost perfectly every time in order for cells to remain healthy.
Rachel Green at the School of Medicine and Howard Hughes Medical Institute has discovered a previously unknown proofreading step that cuts down on some of these possible errors.
Translation requires an extremely high degree of accuracy and precision due to the harmful effects that can result from an improperly manufactured protein. Such mistakes can cause a large range of abnormalities, sometimes unnoticeable and sometimes drastic.
Using a bacterial model system, Green's group has discovered that errors in translation can be corrected right at the source: in the ribsosome, the tiny cellular machine that matches up the messenger RNA code with its appropriate protein counterpart.
"What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress - end of story. There's no second chance," Green said in a university press release.
Proteins are made of strings of amino acids, a group of 20 chemical building blocks that can be arranged in any order. The order of amino acids determines the shape and therefore the function of the resulting protein.
The nucleic acids, DNA and RNA, tell the cell how to arrange those amino acids by using a triplet code: Every three "letters" of nucleic acid tells the cell to place one specific amino acid into a growing protein chain. Every amino acid has one or more unique triplets.
The ribosome is where this translation from gene to protein takes place. A copy of a specific protein's genetic code is transferred from DNA onto a short stretch of nucleic acid called messenger RNA, or mRNA.
The mRNA travels to the ribosome, where each triplet of the code is matched up, in turn, to the appropriate amino acid.
This matching takes place in the first of three slots in the ribosome, called the "A" site, and it is at this very first spot that the ribosome is able to proofread its product.
Using a bacterial model system, Green and her lab have shown that, when an inappropriate amino acid attaches to the A site of the ribosome, the process of protein synthesis is promptly terminated to prevent wasteful production of a potentially harmful protein.
The key detail to this newfound discovery is the fact that this proofreading mechanism occurs after the formation of the peptide bond that links the amino acids in the growing chain.
When the ribosome realizes that it has accepted the wrong amino acid in translating a segment of mRNA, it releases the protein 10,000 times faster than it would normally release a protein that had been accurately translated by the ribosome. This speed reflects the fidelity or accuracy of the process.
Protein synthesis is a vital part of the microbiological aspect of the workings of the human body. The DNA encoded in the genes of the cell is translated into proteins that aid in the successful completion of many essential functions, including energy production and waste excretion.
Protein synthesis gone awry can result in catastrophic damages to the human cell and, as a result, to the rest of the body.
This attention to detail and accuracy that is an innate quality of the ribosome is evidence of the amazing self-corrective abilities of living cells.
"The cell is a wasteful system in that it makes something and then says, forget it, throw it out. But it's evidently worth the waste to increase fidelity. There are places in life where fidelity matters," Green said.
