Researchers have identified a unique mechanism in bacteria that could help in the development of new antibiotics for diseases, such as AIDS, and soft tissue infections, according to a new study.
The study, conducted by researchers from Florida Atlantic University’s Charles E. Schmidt College of Medicine, is published online in the Journal of Biological Chemistry.
According to Ravi K. Alluri, a pre-doctoral student in the department of biomedical science and Dr. Zhongwei Li, Ph.D., associate professor of biomedical science in FAU’s Charles E. Schmidt College of Medicine, every organism lives on the same principle that genes direct the production of proteins.
Transfer RNA (tRNA) is an adaptor molecule that is made up of RNA (typically 73 to 93 nucleotides in length), which is used by all living organisms to bridge the four-letter genetic code (ACGU) in messenger RNA (mRNA) with the twenty-letter code of amino acids in proteins. The team highlights that this process relies on tRNAs as a necessary component of protein translation, and are initially produced as a precursor that feature an extra part at the 5′ and 3′ end, and sometimes also in the middle. These extra parts have to be removed by RNA processing before tRNA can function during the production of protein.
The processing of the tRNAs 3′ end is considerably more complicated and has only recently been revealed in some organisms. Organisms, which contain a cell nucleus like humans, seem to process tRNAs 3′ end in a similar way. For the tRNA to carry building blocks for proteins, it has to be processed entirely.
Alluri remarked: “Intriguingly, bacteria appear to process the 3′ end of tRNA very differently. And we are still trying to reveal the various enzymes called RNases, which remove the 3′ extra parts of tRNA precursors.”
He explains that whilst some of the RNases cut the RNA in the middle, others trim the RNA from the 3′ end. The majority of the bacterial pathways require multiple RNases to complete tRNA 3′ processing.
Li explained: “Knowing how tRNA is processed in different types of bacteria is important not only for understanding how bacteria live, but also for developing novel antibiotics that specifically control bacterial pathogens.”
Alluri and Li’s current work is based on the bacterium Mycoplasma genitalium, which is the second smallest pathogen that is known as a free-living organism believed of causing infertility. Mycoplasma genitalium’s genome only contains about 10% of the genes that have been discovered in other common bacteria, but it contains none of the known RNases for tRNA 3′ processing and therefore needs to use a different RNase to do so.
Alluri states:
“What we have discovered with Mycoplasma genitalium is that it uses a completely different RNase called RNase R to process the 3′ end of tRNA. RNase R can trim the 3′ extra part of a tRNA precursor to make a ‘functional’ tRNA. It is even smart enough to recognize some structural features in the tRNA and tell where the trimming has to stop without harming the mature tRNA.”
A novel mechanism of tRNA 3′ processing is RNase R’s ability to entirely remove the 3′ extra RNA bases in a single trimming reaction. Other mycoplasmas commonly have small genomes and tend to possibly process tRNA in the same way. The fact that only one enzyme is required to execute this complicated task saves genetic resources for mycoplasmas.
Li declared: “Importantly, blocking the function of RNase R in mycoplasmas can stop protein production and kill the bacteria, making RNase R an excellent target of new antibiotics for treatment of mycoplasma infection.”
Written by Grace Rattue