Gene Function

Topics on this page: 

The chromosomes within our cells contain an enormous amount of information. It is estimated that humans have somewhere around 30,000 genes. Each gene codes for an RNAAlso: ribonucleic acid. RNA is a polymer comprised of the nucleotides A, C, G and U. RNA is the working form of our genetic information. RNA is produced via the process of transcription. Some RNA is used to help build ribosomes (rRNA) and some (mRNA) are used to guide the formation of proteins. Other forms of RNA are used to perform specialized functions in the nucleus. molecule that is either used directly or used as a guide for the formation of a proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. such as the insulinA protein hormone secreted by the pancreas. Insulin controls glucose levels in the body by increasing uptake of glucose into cells of the body. Insulin also stimulates the formation of glycogen and alters fat and protein metabolism. shown earlier. Information in our cells generally flows in a predictable order from the storage form of the information (DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. ) through the working form (RNA) into the final product (protein). Further information on the topics on this page can also be found in most introductory Biology textbooks, we recommend Campbell Biology, 11th edition.1 This pathway is used by all organisms and is diagrammed below.

 

As shown, DNA is used as a guide or template for the production of more DNA. This process, known as replicationThe process by which DNA is duplicated. DNA replication occurs during the S phase (synthesis) of the cell cycle. Many chemotherapy drugs act during DNA replication. Some are incorporated into the newly replicated DNA and cause problems. Others interfere with enzymes necessary for DNA replication. See topoisomerase., is addressed here.

The process in which particular sections of DNA (genes) are used to produce RNA is known as transcription. We will cover transcription in some detail because alterations in the transcription of certain genes are very important in the development of cancer.

The set of genes that are 'on' at any given time is critical. The variable environment in which we live means that different genes need to be 'on' at different times. For example, if a meal contains large amounts of lactose, a sugar found in milk, then our bodies respond by turning on (transcribing) the genes that lead to the production of enzymes that break down lactose. If a different sugar or nutrient is present, the correct genes need to be turned on to process it.

Transcription 

The goal of transcription is to make an RNA copy of a gene. This RNA can direct the formation of a protein or be used directly in the cell. All cells with a nucleusPlural, nuclei. A subcellular organelle that contains the chromosomes. Present in eukaryotic cells, the nucleus is surrounded by the nuclear envelope. Within the nucleus is a region called the nucleolus in which the parts of ribosomes are constructed. The nuclear pores allow for the import and export of materials. contain the same exact genetic information. As discussed, only a small percentage of the genes are actually being used to make RNA at any given time in a particular cell. The transcription process is very tightly regulated in normal cells.

  • Genes must be transcribed at the correct time.
  • The RNA produced from a gene must be made in the correct amount.
  • ONLY the required genes should to be transcribed.
  • Turning transcription off is just as important as turning it on.

You can picture this as a sophisticated production line, like you would find in a factory. You would want the assembly line working when you needed the product and shut down when you no longer needed the product.

Human chromosomes contain an enormous amount of information. Each chromosomeA long DNA molecule containing genetic information (genes). Humans have 46 chromosomes. One set of 23 is inherited from each parent. A full set of chromosomes is present in the nucleus of each human cell. is composed of a single extremely long piece of DNA comprised of millions of nucleotides. An individual gene occupies just a small stretch of a chromosome.

Shown in the animation below is the organization of the DNA in a chromosome. The DNA is tightly coiled and looped to take up less space, just like winding thread on a spool. The chromosome shown below has been copied or replicated and has a characteristic X shape. Chromosomes look like this prior to cell division.

 

Steps of Transcription

In order for transcription to work, there must be some way of identifying where the process should start and stop. This is accomplished by special proteins, which bind to the start of genes that are to be transcribed. These proteins are called transcription factors.

The process of transcription is divided into several steps:

  1. A transcription factor recognizes the start site (promoterThe portion of a gene that controls when and how much that particular gene will be expressed (transcribed). Promoters are likened to an on/off switch that determines the activity of a gene. Promoters do not control gene activity themselves, they work by binding to proteins called transcription factors. The transcription factors act as flags to wave down the enzymes (RNA polymerases) that make RNA copies of the genes. Changes (mutations) in the promoter portion of a gene can lead to disruptions in the regulation of gene expression. These changes are often seen in cancer.) of a gene that is to be transcribed.

  2. The enzymeA protein that speeds up the process of chemical reactions in the body without becoming altered in the process. Almost every biological process is driven by the activity of enzymes. Without enzyme catalysts, the complex reactions that build and break down cell parts would not happen at a rate compatible with life. Enzyme names usually describe the reaction that is being catalyzed and all of them end in -ase. that makes the RNA (RNA polymerase) binds to the transcription factor and recognizes the start region.

  3. The enzyme proceeds down the DNA making a copy until the end of the gene is reached.

  4. The enzyme falls off and the RNA is released. This copying process may be repeated numerous times.

  5. If the RNA is one that codes for a protein, it will leave the nucleus and enter the cytosolThe semi-liquid portion of the cell outside the nucleus, excluding the organelles. Compare to cytoplasm..

 

Remember that the gene depicted above is actually a stretch of nucleotides along a DNA molecule (the chromosome).

The inappropriate activity of transcription factors has been identified in almost all types of cancer known. Since these factors are essential to the orderly activities of a cell, a misbehaving component can have important effects for all of the other parts of the cell. Revisiting the production line analogy, a misbehaving transcription factor might lead to the assembly line being on when it is not supposed to, creating too much product. Alternatively, the line might not be on when it is needed, leading to a deficit of a particular product.

Transcription Factors 

Some examples of transcription factors that malfunction in human cancers are:

  • p53A tumor suppressor gene that is mutated in over 50% of cancers of all types. The p53 protein is a transcription factor that controls entry into the cell division cycle. Many signals about the health of a cell are relayed to the p53 protein. This results in a decision by the cell as to whether or not cell division should occur. If the cell is damaged and can not be repaired, the p53 protein is involved in triggering a chain of events that causes the cell to kill itself in a process termed apoptosis. Cells defective for p53 do not have these controls and tend to divide even when conditions are not favorable. Like all tumor suppressors, the p53 gene is normally involved in slowing or monitoring cell division. (TP53)- The gene that codes for the p53 transcription factorA molecule, usually a protein, that binds to DNA at the start of a gene, enabling that gene to be transcribed (copied) to form an RNA molecule. Transcription factors bind to specific parts of genes called promoters, so called because they promote transcription. Transcription factor binding to gene promoters is critical for regulation of the process. Since transcription factors ultimately control what genes are turned 'on' at any given time, they are essential for the proper functioning of the cell. A wide range of transcription factors are known to be associated with cancer. Changes, or mutations, in these genes leads to a deregulation of the whole process. Some key transcription factors are the p53 and Rb proteins. (protein) is mutated in over half of all cancers of any type. The protein that the p53 gene codes for is important because it controls the transcription of genes that are involved in causing cells to divide. More information on the p53 gene can be found in the section on tumor suppressors.
  • RbA tumor suppressor. The Rb gene is mutated in many different cancers but was initially described due to its role in the development of an eye cancer, retinoblastoma, which usually strikes young children. The protein product of the gene is a transcription factor that controls the expression of genes important in driving cells into the division process. - The protein product of this gene is a transcription factor with an interesting function. It actually works by blocking other transcription factors. In this way, Rb prevents transcription of key genes required for cell division to progress. Initially described as a gene mutated in retinoblastomaA cancer of the retina. Found most often in small children; this disease has been linked to the inheritance of mutated copies of the Rb tumor suppressor gene. For more information, see the entries on Rb and Tumor Suppressor., a cancer of the eye from which the gene derives its name, the Rb protein is now known to play a role in many different cancer types. More information on the Rb gene can be found in the section on tumor suppressors.
  • The estrogenA steroid sex hormone. Estrogen's structure is closely related to cholesterol. Produced by the ovaries, estrogen has effects on the reproductive, cardiovascular and skeletal systems. Estrogen is also a growth factor for some types of cells, including breast cells. Inhibitors of estrogen function such as tamoxifen and arimidex are used to block the growth effects of estrogen. See also, estrogen receptor. receptor (ERThe endoplasmic reticulum. A large subcellular network of membranes within the cell. The ER membrane, an extension of the outer nuclear membrane, has two structurally and functionally distinct regions: Rough ER (RER) and Smooth ER (SER). The RER ( the portion closer to the nucleus) has a 'rough' appearance due to ribosomes attached to the surface of the membrane. Ribosomes attached to the ER are producing proteins that are to be released from the cell. Smooth ER (SER) appears smooth and is devoid of ribosomes. SER functions include the detoxification of drugs, the production of steroid hormones and the formation of membrane components. Molecules produced by the RER and SER can be packaged into vesicles and sent to other locations in the cell or to the outside of the cell.) - This protein binds to estrogen that enters the cell. Estrogen is a steroidA type of lipid. Steroids are composed of four carbon rings fused to form one flat (planar) molecule. Examples of steroids include cholesterol, testosterone and estrogen. (lipidA class of biomolecule. Lipids all share the common feature of being hydrophobic . Lipids are one of four classes of biomolecules that make up the majority of the materials in our cells. Other classes are proteins, carbohydrates and nucleic acids.) hormoneA chemical produced by cells that alters the activity of other cells. The chemicals may be lipids, such as testosterone and estrogen or proteins like insulin. Hormones may act at locations far from their site of origin. Estrogen, for example, is produced primarily by cells in the ovaries but acts on cells in the breast and elsewhere. produced by the ovaries. The combination of protein and hormone then acts as a transcription factor to turn on genes that enable the target cells to divide. The receptor is active in the cells of the female reproductive organs, such as breasts and ovaries. Because of this, estrogen is recognized as a factor that enhances the growth of certain cancers arising in these tissues.

The mechanism of estrogen action is shown below.

 

The small green ball represents estrogen. It is a small hydrophobicDescribes molecules which do not interact with water or other polar molecules. The lipid hormones and fat are examples of hydrophobic molecules. From hydro, water and phobos, fearing molecule and it enters cells by crossing through the lipid membrane. Once in the cell, the estrogen binds to its receptor (colored orange) and the complex binds to DNA in the nucleus causing genes to be transcribed.

Several drugs have been developed to try to block the gene-activating function of estrogen. A commonly prescribed example is tamoxifen, a drug that partially inhibits the activity of estrogen. Tamoxifen is colored pink in the animation below.

 

These drugs should slow the growth of cancers that are growing in response to the presence of estrogen and its receptor. More information on estrogen receptors and cancer can be found in the section on cancer treatments.

The importance of transcription factors to the division of cells has been stressed several times. Cancer results from uncontrolled cell division so the next process discussed is cell division. It is important to understand how this process normally functions so that we can appreciate what happens when things go wrong.

Translation

After the messenger RNA (mRNAMessenger RNA, an RNA molecule is a copy of a particular gene that is used in the production of a protein. Messenger RNA is produced in the nucleus via the process of transcription and is exported through holes or pores in the nuclear envelope into the cytoplasm. mRNA then attaches to a ribosome where the encoded message is read to produce a protein in the process termed translation.) is produced through the transcription process just described, the mRNA is processed in the nucleus and then released into the cytosol.

The mRNA is then recognized by the ribosomal subunits present in the cytosol and the message is 'read' by the ribosomeThe organelle that is responsible for the production of protein. Ribosomes are comprised of two subunits that are synthesized in the nucleus at the nucleolus. Ribosomes bind to mRNA and use the information encoded in the RNA to synthesize a protein. Since the mRNA is copied from the gene in the DNA, it is really the DNA that encodes the information. to produce a protein. The information for the direction of protein formation is encoded in the sequence of nucleotides that make up the mRNA. Groups of three nucleotides (called codons) are 'read' by the ribosome and lead to the addition of a particular amino acidA monomer building block used to build proteins. There are many amino acids but only about twenty different kinds are found in most proteins. into the growing polypeptideA relatively short string of amino acids. (protein). The process is depicted schematically in the animation below.

 

After the protein is formed it acquires its active folded state and is able to perform its functions in the cell. The proper folding, transportation, activity and eventual destruction of proteins are all highly regulated processes.

The genes that control these processes are often damaged and not functioning properly in cancer cells.

More information on this topic may be found in Chapter 1 of The Biology of Cancer by Robert A. Weinberg.

Gene Function Summary

The Central Dogma

  • The DNA in our chromosomes contains genes that get transcribed into RNA.
  • There are several different types of RNA (tRNA, mRNA, rRNA, etc.). They are composed of the same building blocks but have different functions, locations and structures.
  • Messenger RNA (mRNA) may be translated into a protein. The standard information flow is:
    • DNA→RNA→Protein
  • The set of genes that are 'on' at any given time is critical. Different genes need to be 'on' at different times depending on the needs and functions of any particular cell.

Transcription

  • The goal of transcription is to make an RNA copy of a gene.
  • Transcription factors bind to the starting point of genes in order to identify the spot where transcription begins.
  • p53, Rb, the estrogen receptorA protein located within cells that binds estrogen. The protein:estrogen complex then binds to DNA to increase the transcription of certain genes, and therefore is a type of transcription factor. The estrogen receptor is the target of the anticancer drug tamoxifen. By binding to the estrogen receptor tamoxifen blocks the growth promoting effects of the hormone. May be abbreviated as ER. are all transcription factors that malfunction in cancers.
  • The process of transcription is divided into several distinct steps:
    1. Transcription factor recognizes and binds to a gene's start site (promoter).
    2. An RNA-making enzyme (RNA polymeraseThe enzyme that produces RNA during the process of transcription.) binds to the transcription factor.
    3. The enzyme makes an RNA copy of the gene.
    4. The enzyme falls off and the RNA is released.
    5. The RNA will either remain in the nucleus or it will exit into the cytosol.

Translation

  • The goal of translation is to make a protein using the information encoded in mRNA.
  • The process of translation is divided into several steps:
    1. mRNA leaves the nucleus and is recognized and bound by ribosomal subunits in the cytosol.
    2. The ribosome 'reads' the RNA three nucleotides (one codonA string of three adjacent nucleotides along a messenger RNA (mRNA) molecule that encodes a single amino acid. Ribosomes are able to 'read' the encoded message in an mRNA and synthesize proteins from amino acids present in the cell.) at a time.
    3. The ribosome inserts the amino acid corresponding to the codon into the growing protein.
    4. The ribosome encounters a stop codon and terminates protein synthesis.
    5. The protein enters a highly regulated folding process and obtains a fully folded structure.
  • Genes that control the proper folding, transportation, activity and eventual destruction of proteins are often damaged or malfunctioning in cancer.
  • 1. Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2017). Campbell Biology (11th ed.). Pearson.