Publication Date

5-2015

Advisor(s)

Michael A. McAlear

Department

Molecular Biology & Biochemistry

Language

English

Abstract

Cellular development, growth and division hinge on the coordinated expression of large sets of genes whose products regulate and promote a wide variety of biosynthetic pathways. The production of ribosomes is a critical aspect of cell cycle progression, due both to the function of ribosomes in protein synthesis as well as the large metabolic cost ribosome production imposes on the cell. Ribosome biogenesis requires the coordinated expression of three distinct genetic regulons that are necessary to produce the 78 ribosomal proteins (RPs), the 4 mature rRNAs, as well as the rRNA and ribosomal biogenesis (RRB) genes whose products are involved in the assembly and processing of the final ribosome. Interestingly, both the RRB and RP regulons are significantly enriched for tightly co-regulated adjacent gene pairs. Genetic expression analysis of the convergent MPP10-YJR003C RRB gene pair revealed that the promoter of MPP10 mediates the transcriptional co-regulation of the gene pair. Replacement of YJR003C with LEU2 or the fluorescent reporter CFP reveals that the corepression of the MPP10-YJR003C gene pair under heat shock is not dependent on the sequences of the YJR003C open reading frame. Subsequent investigations into adjacent gene regulation of the RP gene pair RPS27A-RSM22 reveals that cis-mutations in the promoter of RPS27A can have differential effects on the expression of RSM22. This suggests that adjacent gene co-regulation may be an evolutionarily conserved tool for coordinated gene expression over multiple biosynthetic regulons.

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