The control of gene expression by eukaryotic ribonucleases

Project Summary/Abstract RNA processing and degradation mechanisms play critical functions in the control of gene expression. Not only do they regulate global transcripts abundance, but they also provide quality control mechanisms to eliminate improperly processed or mis-localized transcripts. Work in our laboratory focuses on two main aspects of RNA-based regulatory processes. The first axis of research is focused on the function of nuclear ribonucleases and of nuclear RNA degradation pathways. Nuclear RNA processing and degradation by the RNA exosome, RNase III and the Rex exonucleases play important roles in ribosome biogenesis and in controlling expression of genes in response to stress. Work presented in this proposal will focus on determining the function of nuclear ribonucleases on regulating the expression of key chromatin remodeling factors during stress and on identifying the role of the cancer-linked ribonuclease Rexo4 in mammalian ribosomal RNA processing. The second area of focus of our group is to understand the impact of splicing inactivation on global gene expression. We have analyzed the function of splicing factors in vivo using RNA sequencing and shown that splicing inactivation results in the accumulation of hybrid mRNA-snoRNA (hmsnoRNAs) species which accumulate in the cytoplasm. We will continue these studies by investigating the function of several conserved splicing factors in global gene expression and by analyzing the global impact of splicing inactivation on the proteome, including the translation of hmsnoRNAs. Overall, the proposed studies are expected to have a high impact on our understanding of the mechanisms by which post-transcriptional processes globally regulate gene expression.