Investigating the Role of Long Non-Coding RNAs and RNA Helicase Dbp2 in Gene Regulation
Long non-coding RNAs (lncRNAs) are RNA Polymerase II products that lack an open reading frame and are longer than 200 nucleotides. Emerging evidences suggest that many lncRNAs function in gene regulation of protein-coding genes, the mechanisms of which, however, are largely unknown. In an effort to characterize the biological roles of DEAD-box RNA helicase, my colleagues and I uncovered a role for the GAL lncRNAs in promoting GAL protein-coding gene activation and the DEAD-box protein Dbp2 antagonizes this effect. We also found that Dbp2 promotes the association of Cyc8 co-repressor to the chromatin, presumably through antagonizing lncRNA-DNA hybrid formation at the GAL genes, thereby repressing the induction of the GAL genes upon a switch to galactose. My following work revealed that DBP2 maintains CYC8-dependent repression genome-wide, particularly at the glucose-repressed genes. Taken together, these findings suggest that Dbp2 integrates gene expression network with metabolic program through regulating Cyc8-targeted genes. The Warburg effect in tumor cells shares a lot of similarities with the preference of Saccharomyces cerevisiae in fermenting glucose into ethanol under aerobic conditions. Therefore, understanding the role for Dbp2 in gene regulatory programs that are responsive to the nutritional status in budding yeast will give us insights on the regulation of metabolic states in mammalian cells.
Tran, Purdue University.
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