[Frontiers in Bioscience 3, d376-398, March 26, 98] |
TRANSCRIPTION BY RNA POLYMERASE I
Katherine M. Hannan, Ross D. Hannan and Lawrence I. Rothblum
Henry Hood Research Program, Department of Molecular and Cellular Physiology, Penn State College of Medicine, Weis Centre for Research, 100 N. Academy Avenue, Danville, PA 17822-2618
Received 3/18/98 Accepted 3/23/98
Protein synthesis is an essential process for all living cells. Cells must govern both the amounts of specific proteins synthesized as well as the total protein synthesized in response to environmental signals and internal programming (1,2,3,4). In cycling cells, this coordination insures successful cell division and daughter cell survival. Alternatively, during terminal differentiation or in response to environmental stress, a cell may withdraw from the cell cycle. In many cases this reduces the need for protein synthesis.
The protein synthetic capacity of a cell is dictated by a number of processes such as mRNA availability, efficiency of translation, availability of translation factors or the number of ribosomes. The evidence accumulated to date indicates that the protein synthetic capacity is primarily regulated by the steady state number of ribosomes. This in turn is dictated by the relative rates of ribosome synthesis and degradation (1,2,3,4,5). Ribosome synthesis or biogenesis, is a complex process dependent on the coordinated synthesis of approximately 85 ribosomal proteins, four ribosomal RNAs (rRNA), and their subsequent processing and assembly into mature ribosomes. In contrast, little is known about the process or regulation of ribosome degradation (1,2,3,4).
In the majority of cells, ribosomes are relatively stable thus their cellular content depends largely on the rate of ribosome biogenesis. Experimental evidence so far correlates regulation of ribosome biogenesis to altered rates of rRNA transcription rather than changes in rRNA processing or stability (2,3,4,6). Ribosomal DNA (rDNA) transcription is a major commitment for the cell since it accounts for approximately 40-60% of all cellular transcription and 80% of the steady-state cellular RNA content. The rate of rDNA transcription can vary over a wide range. For example, when Acanthamoeba castellanii encyst, rDNA transcription decreased from 75% to almost 0% of the total cellular transcription (3,7). Indeed rDNA transcription has been shown to be regulated in response to different stages of development or cell cycle, nutritional state and altered environmental or hormonal conditions (1,6,7,8,9,10,11,12,13,14,15,16,17). This illustrates that rDNA transcription, like the expression of cell-cycle specific genes, is a prime example of growth-regulated gene expression.
Present data suggest that cells can utilize a diverse array of mechanisms to coordinate the rate of rDNA transcription with altered cellular requirements for protein synthesis. The relative importance of the various mechanisms to a specific stimulus have not been thoroughly investigated in any single cell. However, the data suggests that these mechanisms tend to be both cell type and stimulus dependent. In many cases the exact molecular mechanism(s) and signaling pathways involved in regulating rDNA transcription are not well understood. Since the regulation of rDNA transcription is a critical component of cellular homeostasis, it is important for us to understand and characterize the process.