Unlike replication of the complete genome, which is essential for cellular propagation, not all genes need to be transcribed in a particular cell for its survival. Synthesis of mRNA is required for generation of proteins. Because not all proteins are required at all times for cellular survival and metabolism, both in prokaryotes and eukaryotes, and many proteins are expressed only in specific stages of development and differentiation in higher eukaryotes, a gene’s transcription is often highly regulated. Furthermore, the stability ofmRNAs and the proteins they encode vary over a wide range. Thus, different mRNAs are not made at the same rate. Additionally, the bulk of RNA, and in fact a large fraction of the cell mass, consists of ribosomal and transfer RNAs needed for carrying out protein synthesis. Both ribosomal and transfer RNAs are extremely stable.
Regulation of transcription, first investigated in bacterial viruses, primarily in E. coli, an intestinal microbe and its bacteriophage λ, is the foundation of molecular genetics. The ease of generating and manipulating mutants of various genes in E. coli and λ led to the discovery of repressors, which are proteins that bind to operator sequences of genes and turn off transcription. The genes that were originally studied encode enzymes for sugar (lactose and galactose) metabolism. Inactivation of these genes and their expression could be studied because the proteins are not essential for bacterial survival. An activator needed for expression of lactose-metabolizing β-galactosidase was identified; it is downregulated in the presence of glucose (“glucose effect”) and upregulated by binding to 3´-5´ cyclic AMP.
Significant advances in elucidating the mechanism of transcriptional regulation came from the life cycle studies of the lysogenic λ virus, whose virus-specific proteins are not expressed in the lysogenic state, when its duplex DNA genome is linearly integrated in the host chromosome. Here again, both positive and negative regulatory mechanisms are in play to fine tune the expression of genes from a low maintenance level during lysogeny to large-scale expression of the viral genome when the lysogenic virus enters the lytic phase of growth and exploits the host cell synthetic machinery for replication of its own viral DNA, RNA, and proteins.
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