Porth's Essentials of Pathophysiology, 4e

94

Cell and Tissue Function

U N I T 1

specific amino acid sequence or to split the molecule into smaller chains. As an example, the two chains that make up the circulating active insulin molecule, one contain- ing 21 and the other 30 amino acids, were originally part of an 82-amino-acid proinsulin molecule. Regulation of Gene Expression Only about 2% of the genome encodes instructions for synthesis of proteins. Although researchers are still learning about the functions of the other 98% of DNA, it is now believed to consist of sequences that code for the production of certain types of regulatory RNA, including RNA involved in the splicing process dis- cussed earlier. Some of the remaining genes are involved in regulation of other genes; whereas others may play a role in regulating various nuclear or cytoplasmic func- tions. The degree to which a gene or particular group of genes is active is called gene expression . A phenomenon termed induction is an important process by which gene expression is increased. Gene repression is a process by which a regulatory gene acts to reduce or prevent gene expression. Activator and repressor sites commonly monitor levels of the synthesized product and regulate gene transcription through a negative feedback mecha- nism. Whenever product levels decrease, gene transcrip- tion is increased, and when product levels increase, gene transcription is repressed. Although control of gene expression can occur in multiple steps, many regulatory events occur at the transcription level. As noted earlier, the initiation and regulation of transcription require the collaboration of a battery of proteins collectively termed transcrip- tion factors . After binding to their own specific DNA region, transcription factors can function to increase or decrease transcriptional activity of the genes. The role of transcription factors in gene expression explains why neurons and liver cells that have the same DNA in their nuclei nevertheless have completely different structures and functions. Moreover, some transcription factors activate genes only at specific stages of development. For example, the PAX family of transcription factors is involved in the development of such embryonic tissues as the eye and portions of the nervous system.

Introns

EXON 3 13 EXON 1 11 EXON 2 12 EXON 4 14 EXON 5

Messenger RNA with introns

Messenger RNA with introns removed

Exon splicing in cell A

Exon splicing in cell B

at a time. After the first part of the mRNA is read by the first ribosome, it moves onto a second and a third. As a result, ribosomes that are actively involved in protein synthesis are often found in clusters called polyribosomes . The process of translation is not over when the genetic code has been used to create the sequence of amino acids that constitute a protein. To be useful to a cell, this new polypeptide chain must be folded up into its unique three- dimensional conformation. The folding of many proteins is made more efficient by special classes of proteins called molecular chaperones . Typically, the function of a chap- erone is to assist a newly synthesized polypeptide chain to attain a functional conformation as a new protein and then to assist the protein’s arrival at the site in the cell where the protein carries out its function. Molecular chap- erones also assist in preventing the misfolding of existing proteins. Disruption of chaperoning mechanisms causes intracellular molecules to become denatured and insolu- ble. These denatured proteins tend to stick to one another, precipitate, and form inclusion bodies. The development of inclusion bodies is a common pathologic process in Parkinson, Alzheimer, and Huntington diseases. A newly synthesized polypeptide chain may also need to combine with one or more polypeptide chains from the same or an adjacent chromosome, bind small cofactors for its activity, or undergo appropriate enzyme modification. During the posttranslation process, two or more peptide chains may combine to form a single product. For example, two α -globin chains and two β -globin chains combine to form the hemoglobin protein in red blood cells (see Chapter 13). The protein prod- ucts may also be modified chemically by the addition of various types of functional groups. For example, fatty acids may be added, providing hydrophobic regions for attachment to cell membranes. Other modifications may involve cleavage of the protein, either to remove a FIGURE 5-5. Ribonucleic acid (RNA) processing. In different cells, an RNA strand may eventually produce different proteins depending on the sequencing of exons during gene splicing. This variation allows a gene to code for more than one protein. (Courtesy of EdwardW. Carroll.)

SUMMARY CONCEPTS

■■ Genes are the fundamental unit of information storage in the cell.They code for the assembly of the proteins made by the cell and therefore control inheritance and day-to-day cell function. ■■ Although every cell in the body contains the same basic genetic information, cells from our body express their genetic information differently, and can therefore differ vastly in their appearance, structure, and function.