Controlling inflammation Excessive inflammation can lead to chronic diseases such as cancer and inflammatory bowel diseases. How inflammation can be regulated is key to developing possible therapies for these diseases. Health © Thinkstock Inflammation is the body’s attempt to protect itself from the effects of damaged cells, irritants and pathogens. The production of molecules required for the inflammatory response is tightly regulated. DNA codes for proteins using RNA as a blueprint to transmit each code into the cytoplasm where the proteins are assembled. This suggests that regulation of inflammation may occur at the RNA.Proteins that attach to RNA – RNA binding proteins (RBPs) -- may regulate inflammation by forming protein complexes. In particular, the RBP human antigen R (HuR) is an important modulator of messenger RNA (mRNA) function. A very important protein in cell function, HuR exists in the cytoplasm where it stabilises many mRNAs.The EU-funded 'Nuclear HuR-hnRNP interactions in post-transcriptional regulation of inflammatory gene expression ' (NRNPS & INFLAMMATION) project studied the role of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes.Previous research by one of the partners has also shown that over-expressed HuR in the nucleus represses translation of specific inflammatory mRNAs and lessens acute inflammatory reactions. In the nucleus, it helps regulate gene expression after transcription through interaction with hnRNPs.A first in the research world, the scientists set up a genome-wide approach technique. The photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) method allows the identification of the RNA involved and determines the location of protein attachment on the RNA.Using PAR-CLIP, the researchers identified RNA targets of HuR that are altered during inflammation. Moreover, how HuR RNPs behave at different mRNA sites has shed light on immune response mechanisms. Also identified are aberrations in mRNA that are linked to shortage of HuR in diseases such as inflammatory bowel disease and intestinal cancer.Knock-down experiments have demonstrated that some HuR interactions result in pro-inflammation while others have immunoregulatory effects. It is anticipated that PAR-CLIP can be used in the analysis of engineered transgenic systems and assessment of their functions.Identifying new ways to regulate and control chronic inflammatory dysfunction promises to open up novel therapies for rheumatoid arthritis, many cancers, hay fever and atherosclerosis. NRNPS & INFLAMMATION technologies can also be used for disease monitoring. Keywords Chronic inflammation, disease, RNA binding protein, human antigen R, PAR-CLIP
