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RNA binding proteins and inflammation
The expression of inflammatory mRNAs is under the control of numerous
regulatory mechanisms that respond rapidly to stimulation from evading
pathogens but also define the time and the extent of protein-synthesis
as to prevent inflammatory disease. Such mechanisms include the
post-transcriptional modulation of mRNA stability within a cell and its
capacity to be translated in response to inflammatory stimuli.
It appears that inflammatory post-transcriptional control proceeds
through the dynamic interactions of mRNA structures residing in
inflammatory mRNAs and selective RNA binding proteins that recognize
these structures. In the September 16th issue of Molecular Cell, the
group of Dimitris Kontoyiannis at the Institute of Immunology of
the BSRC “Fleming” provide in vivo evidence on the organization of
post-transcriptional networks and the clinical significance of
modulating the functions of an RNA binding protein named HuR. The group
has employed a drug-induced transgenic approach in the mouse to perturb
the levels of HuR in cells that “sense” infection and tissue damage and
orchestrate the inflammatory response, i.e. the macrophages. The group
made the unexpected observation that the inducible overexpression of HuR
reduced inflammatory processes and blocked a pathogenic hepatitis
reaction. Through a series of transgenic, cellular, molecular and
biochemical experiments, the group showed that HuR binds to specific
inflammatory mRNAs and blocks their induced translation via a synergy
with inhibitory RNA binding proteins. “Our data have direct clinical
relevance and indicate that the pharmacological targeting of
post-transcriptional networks may be beneficial in inflammatory
diseases” said Vicky Katsanou, a member of the group that
supported this work. The PI of the group, Dr Kontoyiannis adds: “There
is a great degree of complexity in the organization of
post-transcriptional control which we just begin to unravel; however the
importance of these mechanisms in the maintenance of homeostasis and
pathology, suggests that research in this area is expected to provide
better knowledge on the organization of patho-physiological gene
expression networks and provide new alternatives for therapeutic
intervention”.
Relevant Links:
- To visit the D. Kontoyiannis Laboratory’s
web page,
please click here.
- To visit Molecular Cell online,
please click here.
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