The process of protein synthesis does not occur constantly in the cell. Rather, it occurs at intervals followed by periods of genetic “silence.” Thus, the cell regulates and controls the gene expression process.
The control of gene expression may occur at several levels in the cell. For example, genes rarely operate during mitosis, when the DNA fibers shorten and thicken to form chromatin. The inactive chromatin is compacted and tightly coiled, and this coiling regulates access to the genes.
Other levels of gene control can occur during and after transcription. In transcription, certain segments of DNA can increase and accelerate the activity of nearby genes. After transcription has taken place, the mRNA molecule can be altered to regulate gene activity. For example, researchers have found that an mRNA molecule contains many useless bits of RNA that are removed in the production of the final mRNA molecule. These useless bits of nucleic acid are called introns. The remaining pieces of mRNA, called exons, are then spliced to form the final mRNA molecule. Thus, through removal of introns and the retention of exons, the cell can alter the message received from the DNA and control gene expression.
The concept of gene control has been researched thoroughly in bacteria. In these microorganisms, genes have been identified as structural genes, regulator genes, and control genes (or control regions). The three units form a functional unit called the operon.
The operon has been examined in close detail in certain bacteria. Scientists have found, for example, that certain carbohydrates can induce the presence of the enzymes needed to digest those carbohydrates. When lactose is present, bacteria synthesize the enzyme needed to break down the lactose. Lactose acts as the inducer molecule in the following way: In the absence of lactose, a regulator gene produces a repressor, and the repressor binds to a control region called the operator. This binding prevents the structural genes from encoding the enzyme for lactose digestion. When lactose is present, however, it binds to the repressor and thereby removes the repressor at the operator site. With the operator site free, the structural genes are free to produce their lactose-digesting enzyme.
The operon system in bacteria shows how gene expression can occur in relatively simple cells. The gene is inactive until it is needed and is active when it becomes necessary to produce an enzyme. Other methods of gene control are more complex and are currently being researched.
Non-coding RNAs (ncRNAs)
Protein-encoding mRNA is clearly an important molecule, but the other non-coding RNAs (ncRNAs) that control mRNA transcription are increasingly becoming the focus of attention. Two such ncRNA molecules are microRNA and small interfering RNA.
MicroRNAs (miRNAs) are small, single-stranded RNA molecules that, along with associated proteins, bind to complementary sequences in certain mRNA molecules. Once bound, these miRNAs block translation of the mRNA by either physically preventing the ribosome from binding, or by causing the mRNA to degrade. The result—either blocked translation or mRNA degradation— depends on the extent of the base pairing between the miRNA and the target mRNA. Possibly half of human genes are regulated by miRNA.
Small interfering RNAs (siRNAs) are similar in structure and function to miRNAs. RNA interference (RNAi) is a means of disabling a gene by introducing siRNAs into a cell. Researchers employ RNAi to knock out specific genes in order to study their function.
Modification of chromatin structure
Recall that DNA is condensed and packaged with histone proteins into a complex known as chromatin (see Chapter 7). This compact structure helps DNA to fit into the nucleus and also provides opportunity for gene regulation. In order for a gene to be accessed by the transcriptional machinery, it must be “unwound” from the histone proteins. This is facilitated by certain enzymes adding acetyl groups (–COCH3) to the histones (histone acetylation). Alternatively, if a segment of DNA needs to remain unexpressed (such as the inactivated mammalian X chromosomes), a different set of enzymes will add methyl groups (–CH3) to certain bases, thus maintaining DNA’s tightly wound and inaccessible form.
How a cell controls the expression of its genes is almost as important as the genes themselves. Modification of DNA and its associated histone proteins has a profound effect on that gene’s expression. Furthermore, these modifications can be passed on to future generations and thus effect gene expression in progeny. This is called epigenetic inheritance. Alterations in normal modification have also been linked to some cancers, due to inappropriate gene expression.