Structure and mechanism of key nonsense-mediated mRNA decay factor complexes

The genetic information in our bodies is transcribed into a molecule called messenger RNA (mRNA). The mRNA message is translated into proteins which act as catalysts. At times, these mRNAs contain a translation termination signal at the wrong place and has given rise to truncated proteins, some of which are toxic and cause severe disease. The cell has devised a quality-control mechanism, called nonsense-mediated mRNA decay (NMD), to recognise and eliminate faulty mRNAs. Despite its importance, our understanding of key NMD mechanisms remains 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 be the key to this process. We will test it in living cells and in vitro, using electron cryo-microscopy to visualise how these proteins function and how the protein synthesis and the quality-control machinery function in health and disease.