Molecular Mechanisms of NMDFactor Complexes

The genetic information in our bodies is transcribed into a molecule called messenger-RNA. This mRNA message is translated into proteins which catalyse biological function.At times, these mRNAs contain a translation termination signal at the wrong place (a PTC), giving rise to truncated proteins, some of which are toxic and cause severe disease. The cell has devised a vital quality control mechanism, called nonsense-mediated mRNA decay(NMD), to recognise and eliminate such faulty mRNAs. Despite its paramount importance, our understanding of key NMD mechanisms remain elusive. We do not know how the NMD factors orchestrate the vital step of recognising faulty mRNAs.

Recently, we discovered novel NMD factor interactions which may unlock this enigma, which we will now test in living cells and in vitro, e.g. using in vivo biochemistry,crosslinking, mass spectroscopy, structural biology and biophysics to understand how the NMD proteins function and thus reveal their interplay, in health and disease.