Findings from a recent study in ‘messanger RNAs’ and ‘STAR
proteins’ hold promise of helping in designing drugs.
Since many drugs have specific proteins as their targets,
understanding how these targets interact with mRNAs could play a big role
researchers say.
The study published in the journal Scientific Reports, by
researchers from the Indian Institute of Science Education and Research (IISER)
Mohali, dwells on some interesting discoveries on how messenger RNAs (mRNAs)
bind to a class of proteins called ‘STAR proteins’. The study also throws some
insight into the structural changes that these proteins then undergo.
The findings of the study could be used to design mutations
and to identify amino acids that are essential for mRNA binding.
The Ribonucleic Acid (RNA) found in our cells was once
thought of only as a messenger, relaying information from the DNA (the genetic
material), to the ribosomes, to make proteins. The aptly called ‘messenger’
RNAs (mRNAs) do this by binding or sticking to specific protein molecules.
Ribosomes then used this information to produce proteins that are needed by the
body. Recent studies have now shown that RNAs do much more as they also
function as switches, regulators, enzymes and also control many cellular
events.
“Over the last three decades, the
STAR family of proteins has generated lots of interest in scientific community.
Every now and then, there is a new discovery in the role of a STAR protein with
implications in critical functioning of the concerned organism.”, says Dr.
Monika Sharma from the Department of Chemical Sciences, IISER Mohali and author
of the study, who along with C. R. Anirudh, an undergraduate student from IISER
Mohali, did this study.
The research was funded by Department of Science and
Technology (DST), India, through the INSPIRE award and research grant.
Among the various proteins that mRNAs bind to, the STAR
proteins (Signal Transduction and Activation of RNA) are special since they act
as regulators of many processes that are related to cell development. These
proteins are so important that they are found in the genomes of all organisms,
from yeasts to humans, and are preserved in the process of evolution.
Using simulations, the researchers studied the interactions
of mRNA bound complexes and the STAR domain of the QKI protein, a protein found
in mammals. The QKI protein carries genes that are implicated in many diseases
like cancer, neurological disorders such as ataxia, multiple sclerosis and
schizophrenia. They carried out these simulations in the presence and absence
of bound mRNA to understand how mRNA binding influences the STAR domain. They
also studied the changes that occur to the structure of the STAR protein during
the mRNA-STAR binding. They further investigated the process of how the mRNA unbinds
from the STAR domain.
These results agree with other
experimental research on mutagenesis, the process by which certain parts of an
organism's genetic makeup can be changed . “If there is mutation observed in
the QKI protein, one can speculate its effects. For example, whether it is
interfering with the stability of the protein, or hindering the interaction of
proteins with mRNA”, explains Dr. Sharma.
The research suggests that the binding of mRNA is an
interaction between the selection of structures and the way they fit together
with the binding protein partners, in the process, influencing the shape of the
protein. The study could also aid in drug design since many drugs have specific
proteins as their targets and understanding how these targets interact with
mRNAs could play a big role here.
As a next step, the researchers are focusing on studying some
more mRNA-STAR protein interactions. “I am currently pursuing the exact
mechanism of the binding of mRNA with STAR domains using a series of sampling
simulations. In addition, we are looking at what makes this short stretch of
mRNA special, allowing it to bind to the STAR domain using a comparative
analysis of simulations of several cognate mRNA sequences, which binds to these
STAR domains, and non-cognate mRNA sequences, which do not.” says Dr. Sharma on
the future directions of her research.
Source: Researchmatter.in
