Researchers from Florida Atlantic University's Charles E. Schmidt
College of Medicine have identified a unique mechanism in bacteria that
has the potential to serve as a target for developing new antibiotics
for diseases such as AIDS and soft tissue infections including
respiratory and urogenital tracts, which are currently difficult to
treat.
The results of these findings were published in an article titled
"Novel One-step Mechanism for tRNA 3'-End Maturation by the
Exoribonuclease RNase of Mycoplasma gentialium" in the current issue of
the Journal of Biological Chemistry.
Co-authors of the article are 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.
Li and Alluri explain that every organism lives on the same principle
that genes direct the production of proteins. This process depends on a
set of small RNAs called tRNAs that carry the building blocks of
proteins. A tRNA is produced from its gene initially as a precursor that
contains extra parts at each end (5' and 3' ends) and sometimes in the
middle. These extra parts must be removed through RNA processing before
tRNA can work during protein production. The processing of tRNA 5' end
has been known for quite some time and work on this enzyme has received a
Nobel Prize. Processing of the 3' end is much more complicated and has
only been revealed in some organisms more recently. Organisms that have
nucleus in their cells, including humans, appear to process the 3' end
of tRNA in a similar way. A tRNA must be precisely processed before it
can carry a building block for proteins.
"Intriguingly, bacteria appear to process the 3' end of tRNA very
differently," said Alluri. "And we are still trying to reveal the
various enzymes called RNases, which remove the 3' extra parts of tRNA
precursors."
Some of the RNases cut the RNA in the middle, while others trim the
RNA from the 3' end. Most of the bacterial pathways involve multiple
RNases to complete tRNA 3' processing.
"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," said Li.
One such pathogen is the bacterium Mycoplasma genitalium, which is
the second smallest known free-living organism that is thought to cause
infertility. Alluri and Li's current work focuses on this bacterium --
its genome only contains about 10 percent of the genes found in other
common bacteria. Surprisingly, this bacterium contains none of the known
RNases for tRNA 3' processing and hence it has to use a different RNase
to do so.
"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," said Alluri. "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."
The ability of RNase R to completely remove the 3' extra RNA bases in
a single-step trimming reaction represents a novel mechanism of tRNA 3'
processing. Other mycoplasmas generally have small genomes and likely
process tRNA in the same way. Using only one enzyme for this complicated
task saves genetic resources for mycoplasmas.
"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," said Li.
Story Source:
The above story is reprinted from materials provided by Florida Atlantic University, via Newswise.
Courtesy: ScienceDaily
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