Understanding the role of the RNA-binding protein Mmi1 in coupling transcription and RNA processing by the exosome complex. (360G-Wellcome-088359_Z_09_A)

Regulation of gene expression in eukaryotes is integral to establishment of the cell identity and survival. Synthesis of pre-mRNA in eukaryotes is catalyzed by RNA polymerase II (Pol II). The level and quality of RNA is controlled by the RNA gsurveillance h machinery represented by the highly conserved exosome complex of 3'-5' exonucleases, which is therefore responsible for establishing the balance between RNA synthesis and degradation. Recent studies revealed that the exosome has a key role i n RNA metabolism by degrading defective RNAs in both nucleus and cytoplasm. It is also involved in precise trimming of the 3'ends of sn/snoRNA, tRNA and rRNA precursors. However, the mechanisms regulating and targeting exosome activity to its multiple RNA substrates are poorly understood. The proposed research will explore how RNA quality is monitored by investigating the molecular mechanisms involved in regulating the exosome activity in S. cerevisiae. Initially, genetic and biochemical approac hes will be applied to identify potential exosome co-factors. The functional contribution of each co-factor in determining specificity of the exosome complex will be further examined by monitoring RNA processing in vitro and in vivo. This study will be instumental for our understanding of how different expression programs are executed in cells.