19: Regulating the Flow of Information

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All cells, whether single-celled bacteria or components of a complex multicellular organism such as a human, contain every gene in that organism’s genome. However, cells need the products of only some of these genes, and even those that they do need may be needed only under certain conditions. For example, a bacterium does not need the enzymes required to metabolize lactose when its current food source is glucose. Different cell types of multicellular organisms use different subsets of gene products to carry out their various functions—a liver cell does not need the same gene products as a muscle cell.

The relative amounts of each gene product required by a cell can also vary considerably. In an actively growing cell, for example, ribosomes are in high demand and can account for almost half of the cell’s dry weight, whereas only a few molecules of certain DNA repair proteins are required to do the necessary repair job. From an energy standpoint, having all gene products present in the highest possible amounts at all times would overburden the cell, considering the resources required to synthesize RNA and protein. Therefore, the expression of genes must be regulated so that their products are present in the right amount and only when they are needed.

Cells have evolved to respond to environmental changes and to adapt quickly to new growth conditions. This is how organisms can colonize a wide variety of biological habitats. Changing conditions range from variation in the availability and type of food sources to complex developmental regulatory programs in multicellular organisms, for which some gene products may be needed for a surprisingly brief time and in only a few cells.

Gene regulation is also important to the prevention of diseases, including cancer. In multicellular organisms, selective cell proliferation and destruction are critical for maintaining the proper levels of each cell type. The cell division cycle and programmed cell death pathways are exquisitely controlled by genes that promote or prevent these processes in response to cellular signals. When these regulatory genes are compromised, uncontrolled cell division can lead to the development of tumors. For example, p53 is a regulatory gene that plays a role in initiating programmed cell death. Loss-of-function mutations in p53 are found in about 50% of all lung cancers, 70% of colon cancers, and 30% to 50% of breast cancers.

Gene expression can be regulated at many different points in the synthesis of a functional RNA or protein. Transcription initiation is the most widely used regulatory point in both bacteria and eukaryotes, as this is the least costly way to control a gene. Initiation of transcription occurs at the very beginning of the synthetic pathway, before the investment in energy needed to make either RNA or protein. Nevertheless, mechanisms to regulate gene expression are found at virtually every point along the biosynthetic pathway. The points of regulation, shown in Figure 19-1, include (1) transcription initiation, (2) posttranscriptional processing (RNA processing), (3) RNA stability, (4) translation (protein synthesis), (5) protein modification, (6) protein transport, and (7) protein degradation.

It is obviously important for cells to use their resources efficiently and not to waste energy synthesizing gene products that they do not need in a particular growth environment. But just as critical as efficiency is adaptability, and thus control: cells must be able to respond rapidly to changes in the need for various gene products. In other words, cells are control freaks! One could argue that control is ultimately more important than energy efficiency for the cell’s adaptation and survival. Although this point is often lost in discussions of gene regulation, it is central to biology. As you can see from Figure 19-1, and as we discuss in this and the following chapters, some regulatory mechanisms are directed at mRNA or even at the protein products of mRNA translation. Why do cells “waste” their efforts in this way? Such pathways provide a means of rapidly altering the levels of active proteins in response to the cell’s needs. Over the course of evolution, cells and organisms with such capability have won out over those that may have been more energy efficient but were less able to adapt to changing conditions. Thus, gene regulation involves a fine balance between efficiency and adaptability. New and surprising regulatory mechanisms continue to be discovered, and newly discovered posttranscriptional and translational regulatory processes are proving to be highly important, especially in eukaryotes.

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In Chapters 15–18 we learned about the mechanics of transcription and translation, processes critical to the flow of biological information. Now we consider how these processes are regulated by the cell to conserve resources while effectively responding to changing environmental conditions and achieving optimum cell function. This chapter presents some general principles of gene regulation that are common to the mechanisms used by both bacteria and eukaryotes. We start by examining the protein-DNA interactions that hold the key to transcriptional regulation. We then discuss principles of posttranscriptional regulation, to provide a more complete overview of the rich complexity of regulatory mechanisms. Chapter 20 provides a more in-depth look into bacterial gene regulation, and Chapters 21 and 22 address the complex regulation of gene expression in eukaryotes.