We continue our long-term study of the regulation of ribosomal RNA transcription in the yeast, Saccharomyces cerevisiae. Ribosomal RNA is transcribed by RNA polymerase I (po1I) and comprises over half of the total RNA of the cell. Both the cis-acting DNA elements, as well as the trans-acting protein factors which control po1I transcription have largely been identified in past work. The challenge now is to understand how these DNA and protein elements function to produce ribosomal RNA in strict co-ordination with the growth rate of the cell. Because ribosomal RNA production is so important to the economy of the cell, it is subject to regulation at many different levels. Thus, experiments are proposed to study regulation at the level of 1) the polymerase itself, 2) the pre-initiation complex that forms at the promoter, 3) chromatin which must be cleared for the pre-initiation complex to form. Other experiments will survey all of the po1I transcription machinery during a major metabolic shift (glycerol/ethanol to glucose) to determine which of these potential regulatory levels are actually utilized. Ribosomal RNA is a major and essential component of all living cells. Alterations in po1I transcription are not known to be associated with any disease state, but understanding how ribosomal RNA production is co- ordinated with cell growth is one of the major unsolved problems of cell biology.
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