Transcriptome

Related Terms

Active genes, DNA, genome, genomics, microarray, mRNA, nucleic acid, PCR, polymerase chain reaction, transcriptomics, transcriptome, tRNA.

Background

The cell is the unit of life. It contains instructions for building and operating any organism it is a part of, whether a human cell, a plant cell, or a single-cell organism such as a bacterium. Every cell in that life form has the same instructions, but each group of cells uses only a few of those instructions. Brain cells build the brain, lung cells build lungs, and so on. When the building is done, the cells use a new set of instructions to perform their different functions.
Genes, which are located inside of cells, contain the information that controls an organism's development and functions by instructing cells to make new molecules, usually proteins. Genes are passed down from parents to their children.
The genes are carried in a large molecule called DNA (deoxyribonucleic acid). DNA is a very long and complex chemical in the nucleus of the cell, and carries a four-letter code. The code directs the machinery of the cell to perform all the necessary functions in the body.
Much of the code spells out instructions for building every protein in the organism. Proteins are the workers in the body; they do all the construction, make up a good portion of what is built, and perform most of the operations that make up the activities of an organism. There are roughly 30,000 proteins in a human body. Many other codes in the DNA do not provide instructions for making proteins. Some turn genes on, some turn genes off, but most of them are poorly understood at this time. Some proteins make the other non-protein chemicals that the body needs to function.
Chemical signals turn on specific genes in the DNA. These genes become active, making a molecule called messenger RNA (mRNA) exactly as the DNA directs. This is called transcription. The mRNA leaves the nucleus for the cytoplasm, where it meets tiny transfer molecules that carry the building blocks for proteins. These transfer molecules are called transfer RNA (tRNA). There is one tRNA molecule for each of the 20 building blocks needed to build a protein. These building blocks are called amino acids. A protein is simply a string of amino acids.
Special assembly lines, similar to those that make automobiles, gather the amino acids from the tRNA molecules and arrange and assemble them into a protein according to the instructions received from the DNA. This process is called translation. All the genes that are active at a given time, those that are being transcribed, make up the "transcriptome" of the cell or group of cells. The transcriptome is the total number of genes that are active at any given time in a cell or group of cells, while the genome represents every gene in the cell of an entire organism.
Transcriptomics examines the activity level of genes in a given cell group at a particular time. A cell group is a collection of cells, called a tissue, that are doing the same thing, such as making a hormone.

Methods

The transcriptome is the total number of genes that are active at any given time in a cell or group of cells, while the genome represents every gene in the cell of an organism. The study of transcriptomics examines the activity level of genes in a given cell group at a particular time. A cell group is a collection of cells, called a tissue, that performs a function, such as making a hormone.
To find out which genes are active, researchers homogenize a cell or tissue and separate the mRNA because every active gene is making an mRNA molecule. The mRNA molecules are then multiplied many times over by a process called polymerase chain reaction (PCR) until there are enough to identify each one specifically. PCR is a process performed in a laboratory in which one strand of a molecule is copied over and over again until there are hundreds or thousands of copies. This process requires a specific set of ingredients, the same that a cell contains to replicate the nucleic acids DNA and RNA. There must be the protein enzymes that copy the target strand, the smaller chemical components of that strand to serve as building blocks, and a variety of chemicals that encourage the chemical reactions and stabilize the chemical environment. PCR is called a chain reaction because each cycle multiplies the products of the previous cycle. Cycling is controlled by changing the temperature of the chemical reaction.
The identification of each mRNA molecule takes place using another technique called microarray analysis. Microarrays are the most advanced of the currently used techniques because they can test for many different molecules at once. Thousands of chemical markers can be arranged in a single instrument. Each marker changes when it binds with the one mRNA that it is designed to identify. These changes can be seen because a molecule attached to the marker glows under ultraviolet light (fluorescence) gives off light when it reacts with certain other chemicals (chemiluminescence) or is radioactive. When all the mRNA molecules from a cell or group of cells are identified, this list is the transcriptome of the cell or cells being studied.

Research

Because all cells contain the same complete set of instructions, it is important to know which instructions a cell group is working from. This is most important in cancer research because cancer cells read some codes incorrectly, make some proteins they are not supposed to make, and do not make others that they should be making. The result is a cancer instead of a normally functioning tissue.
Transcriptomes as well as genomes from many human, animal, plant, and disease-causing cell lines, such as malaria, are available on the Internet. Scientists use these libraries to identify targets for further research into the mechanism of diseases, for selecting a gene they want to study or modify, for investigating the life functions of commercially useful organisms such as foods, and for many other purposes. For example, vitamin A deficiency is a major cause of blindness in developing countries. Rice is a staple food for most of those afflicted. Identifying the gene from the transcriptome of a cell that makes vitamin A has resulted in transferring that gene to rice. Golden rice, named for its characteristic golden color caused by its beta-carotene content, will prevent millions of cases of blindness.

Implications

Transcriptomics examines the activity of genes in a given cell group at a particular time. Already many of the abnormal proteins found in cancer patients are being targeted by drugs that slow the progress of the cancer. These drugs bind to the proteins and inactivate them. An example is vascular growth factors that promote the growth of blood vessels into a tumor. Without a blood supply, a tumor cannot grow. Transcriptomics identifies which cells are producing which abnormal proteins.
This new frontier of medicine is already bringing results, not only in cancer but also in many chronic conditions such as arthritis and Alzheimer's disease. Rheumatoid arthritis is an inflammatory condition that is caused by overactivity of several inflammatory chemicals. Blocking these chemicals slows the progression of the disease. Progress in Alzheimer's disease is still in the discovery stage, characterizing the nature and origins of the abnormal proteins that cause the brain to lose function. Transcriptomics identifies which abnormal proteins are being produced in each disease state.
Bacteria make enzymes that turn cellulose to sugar. Yeast ferments sugar into ethanol. When these two processes can be sorted out of the relevant transcriptomes and combined into the transcriptome of a single bacterium, ethanol fuel from wood waste and switch grass (weeds) will become economical to produce.
Resistance to the herbicide Roundup? has been genetically engineered into the transcriptome of corn engineered by Monsanto. This corn thrives when all the surrounding weeds are killed by spraying with Roundup?, producing much larger harvests.
Naturally occurring bacteria and other carrion feeders already clean up the environment. Active research on their transcriptomes is seeking to improve the efficiency of cleanup, such as creating a bacterium that consumes oil and that could be harnessed to clean up oil spills.

Limitations

Transcriptomics is in its infancy. It is extremely complex and will take decades to mature. Steps that must be taken include the identification of useful genes to isolate and commercialize them, the identification of harmful genes to cripple them, finding a suitable host for the useful genes, finding an inhibitor of the harmful genes, extensively testing the results until safety and efficacy are assured, and mass producing and marketing the successful products.
Cancers have many abnormalities and many ways of causing damage. Research has shown that cancers invent ways to bypass single drugs, so that using several drugs at once produces better results. A great deal of research is looking for the best combinations of drugs for each type of cancer. Successful treatments are already available for breast cancer, colorectal cancer, lung cancer, ovarian cancer, and leukemia, to name a few. Because genomics and transcriptomics are finding common mechanisms for multiple cancers, these treatments are being used across many types of cancer with promising results.

Future research

Current research in the field of transcriptomics is still mainly about building the library of cell transcriptomes. The few actual treatments and applications that have trickled out are merely the beginning of what is in the pipeline.
Identifying the abnormal activities of a group of cancer cells will eventually be used to repair them, although current success is limited to identifying abnormal metabolic pathways and blocking them. The ability of certain viruses to insert genes into a genome is the principal mechanism for altering the transcriptome of a cell.
Already, many of the abnormal proteins found in cancer patients are being targeted by drugs that slow the progress of the cancer. These drugs bind to the proteins and inactivate them. An example is vascular growth factors that promote the growth of blood vessels into a tumor. Without a blood supply, a tumor cannot grow. Transcriptomics identifies these abnormal proteins.
This new frontier of medicine is already bringing results, not only in cancer but also in many chronic conditions such as arthritis and Alzheimer's disease. Rheumatoid arthritis is an inflammatory condition that is caused by overactivity of several inflammatory chemicals. Blocking these chemicals slows the progression of the disease. Progress in Alzheimer's disease is still in the discovery stage, characterizing the nature and origins of the abnormal proteins that cause the brain to lose function. Transcriptomics identifies abnormal proteins being produced in each disease state so that they can be targeted with drugs.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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