Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA. The process of gene expression is used by all known life – eukaryotes: including multi-cellular organisms, prokaryotes: (bacteria and archaea) and viruses – to generate the macromolecular machinery for life.
Gene structure and gene expression in higher organisms:
Several steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multi-cellular organism.
In genetics gene expression is the most fundamental level at which genotype gives rise to the phenotype. The genetic code is “interpreted” by gene expression, and the properties of the expression products give rise to the organism’s phenotype.
The gene itself is typically a long stretch of DNA and does not perform an active role. It is a blueprint for the production of RNA. The production of RNA copies of the DNA is called transcription, and is performed by RNA polymerase, which adds one RNA nucleotide at a time to a growing RNA strand. This RNA is complementary to the DNA nucleotide being transcribed; i.e. a T on the DNA means an A is added to the RNA. However, in RNA the nitrogen-containing base Uracil is inserted instead of Thymine wherever there is an Adenine on the DNA strand. Therefore, the mRNA complement of a DNA strand reading “TAC” would be transcribed as “AUG”.
Transcription of protein encoding genes creates a primary transcript of RNA at the place where the gene was located. This transcript can be altered before being translated; this is particularly common in eukaryotes. The most common RNA processing is splicing to remove introns. Introns are RNA segments which are not found in the mature RNA, although they can function as precursors, e.g. for snoRNAs, which are RNAs that direct modification of nucleotides in other RNAs. Introns are common in eukaryotic genes but rare in prokaryotes. RNA processing, also known as post-transcriptional modification, can start during transcription, as is the case for splicing, where the spliceosome removes introns from newly formed RNA. Extensive RNA processing may be an evolutionary advantage made possible by the nucleus of eukaryotes. In prokaryotes transcription and translation (see below) happen together whilst in eukaryotes the nuclear membrane separates the two processes giving time for RNA processing to occur.
Translation is the process that takes the information passed from DNA as messenger RNA and turns this into a series of amino acids bound together with peptide bonds. It really is a translation from one code, nucleotide sequence, to another code, amino acid sequence. The ribosome is the site of this action, just as RNA polymerase was the site of mRNA synthesis. The ribosome matches the base sequence on the mRNA in sets of three bases (called codons) to tRNA molecules that have the three complementary bases in their anticodon regions. Again, the base pairing rule is important in this recognition (A binds to U and C binds to G). The ribosome moves along the mRNA, matching 3 base pairs at a time and adding the amino acids to the polypeptide chain. When the ribosome reaches one of the “stop” codes, the ribosome releases both the polypeptide and the mRNA. This polypeptide will twist into its native coformation and begin to act as a protein in the cells metabolism. This may be a binding protein, an enzyme, a membrane channel or transport site, or part of the electron transport chain. This description is for the simplest case such as some examples of bacterial protein synthesis. Eukaryotic cells follow these steps but other control steps and modifications are common.
The steps in translation are:
• The ribosome binds to mRNA at a specific area
• The ribosome starts matching tRNA anticodon sequences to the mRNA codon sequence
• Each time a new tRNA comes into the ribosome, the amino acid that it was carrying gets added to the elongating polypeptide chain
• The ribosome continues until it hits a stop sequence, then it releases the polypeptide and the mRNA
• The polypeptide forms into its native shape and starts acting as a functional protein in the cell
Originally, gene expression profiling was mainly applied in target discovery and validation. However, the initial promise of being able to find new targets easily was not always met. Validation of targets identified through genomics proved to be a lengthy process. Recently, the use of gene expression profiling has been expanded to later stages in the drug discovery pipeline, including pharmacogenomics-based assessment of efficacy and safety of novel compounds. The use of gene expression for clinical applications, such as patient classification and diagnostics, is emerging. Many groups are working on the classification of different types of cancer and on the development of gene expression-based diagnostic tools to select the best treatment. One such recently approved test is Mammaprint by Agendia, which allows predicting the likelihood of breast cancer returning within five to ten years after a women’s initial cancer.
One of the largest challenges in gene expression profiling remains the establishment of good experimental design practices. Optimally, one would like to predefine the technical approach and analysis strategy to address the biological questions of the project. Another challenge is the vast bioinformatics involved with analyzing gene expression data, especially when comparing data from other “omics” technologies, such as proteomics or metabolomics. Currently there are not many tools available that easily allow combining such data, to lead the scientist to biological interpretation and planning of follow-up experiments.
Portions of this article were taken from Wikipedia content on ‘Gene expression’