This is one of several projects available on an MRC funded 4-year multi-disciplinary PhD programme in Human Genetics, Genomics and Disease at the MRC Human Genetics Unit (HGU), part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.
NMD selectively degrades mRNAs harboring premature termination codons (PTCs) but also regulates the abundance of a large number of cellular RNAs. Most studies to date have focused on cytoplasmic NMD; however, we have recently uncovered evidence suggesting the existence of an NMD pathway dedicated to Endoplasmic Reticulum (ER)-localized mRNAs. We will define the subcellular localization of NMD for those transcripts that are translated at the ER, and will identify mRNA targets and novel components of the ER-NMD pathway. We will focus on the physiological role of this novel pathway, as well as on the biological consequences of manipulating its activity.