The role of the nuclear exosome complex in RNA regulation. (360G-Wellcome-106994_Z_15_Z)

Accurate regulation of RNA levels in eukaryotes is integral to many aspects of cellular metabolism including establishment of cell identity and survival. A conserved multisubunit exosome complex of 3'-5' exo- and endonucleases is absolutely essential for maintaining the proper levels of functional RNA and specific elimination of defective RNA in both nucleus and cytoplasm. However, the mechanisms providing specificity to the nuclear exosome complex in targeting specific classes of RNAs are poorl y understood, in contrast to the well-studied regulation of cytoplasmic decay. Understanding of the normal exosome function is of major biomedical importance, as deregulation of the exosome activity is associated with several severe human diseases. We recently discovered several RNA-binding proteins that function by directing the exosome complex to the specific RNA targets in the nucleus. Our aim is to advance the field further by uncovering mechanistically how these factors (exosome regulating factors, ERFs) regulate exosome activity. In the longer term, these new insights will be crucial for our understanding of the key molecular events that mediate cross-talk between transcription, RNA-processing and surveillance machineries to control the fate and function of RNA. Together, these studies will be instrumental to advance our understanding of how accuracy and efficiency of gene expression is achieved in health and disease.