The basics of gene expression

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The basics of gene expression

Information in a biological organism is stored in its genome. The genome of all complex organisms consists of long molecules of DNA made up of chains of nucleotides in a double-helix structure. The basic functional unit of the genome is a gene. The central dogma of molecular biology states that information stored in the DNA of a given gene is transcribed into RNA, which is then translated into proteins (see Figure 1).

**Figure 1:** The Central Dogma. The creation of a protein molecule from a DNA double helix occurs in two stages, transcription and translation. In the transcription stage, the two strands of DNA are separated at the site of the gene, and the RNA polymerase enzyme copies the noncoding strand of DNA into a complementary mRNA strand. The mRNA is then transported from the nucleus to the cytoplasm where it is translated by ribosomes into an amino acid chain.
$\begin{figure} \begin{center} \includegraphics[scale=0.4]{figures/dogma} \end{center} \end{figure}$

Proteins are the fundamental structural and functional units in cells. Each one is specialised to carry fill one of a variety of important roles, such as a structural element, enzyme catalyst or antibody. A large subset of proteins known as transcription factors (TFs) also play a regulatory role, determining when, where and how much a particular gene is expressed into proteins. Because regulatory proteins are themselves the products of expressed genes, they too are under regulatory control, giving rise to complex networks of interacting genes.

This section describes the processes of transcription and translation that mediate the path from DNA to protein in prokaryotic and eukaryotic cells. While the gene expression mechanism in both types of cells is generally very similar, there are several significant differences [121]. In eukaryotic cells, DNA is stored in the nucleus, whereas prokaryotic cells have no nucleus. All complex, multicellular organisms are eukaryotic, and their cells tend to have a considerably higher level of regulatory complexity than single-celled prokaryotic organisms such as bacteria.

Transcription

A gene consists of a regulatory region, which controls when the gene will be activated, and a coding region, which specifies the shape of the protein that will be produced when the gene is activated (see Figure 2). In prokaryotes, the regulatory region is generally located directly upstream of the coding region, whereas in eukaryotes elements of the regulatory region may be located at a considerable distance both upstream and downstream from the coding region. A regulatory region contains binding sites for a number of transcription factors (TFs). Individual TFs may exert either positive or negative control on the activation of a gene, increasing or decreasing its rate of transcription. When the activation conditions for a given gene are fulfilled, a large molecule called RNA Polymerase binds to the TF complex and the DNA in the gene's coding region is unwound. The sequence of nucleotides on the coding strand of the DNA is then used as a template to create a single-stranded messenger RNA (mRNA) molecule [92].

**Figure 2:** Regulation of transcription initiation (the operon model). In the operon model, the operator region of a gene may be bound by a regulator protein, preventing the transcription of structural genes by RNA Polymerase (top). When an inducer molecule is present, it binds to the regulator protein, releasing the operator and allowing RNA polymerase access to transcribe the structural genes (bottom).
$\begin{figure} \begin{center} \includegraphics[scale=0.4]{figures/operon} \end{center} \end{figure}$

In prokaryotes, the coding region is contiguous. In eukaryotes however, the coding region is broken up into a series of coding exons and non-coding introns, which must be spliced out of the initial RNA transcript. A number of other processing mechanisms are also possible at this stage. In many cases, a single eukaryotic gene can be spliced and edited in multiple ways to produce a variety of different protein products [110] (see Figure 3). As the next step of gene expression, translation, occurs in the cytoplasm of the cell, mRNA molecules in eukaryotes must also be transported outside of the cell nucleus.

**Figure 3:** Alternative splicing. In eukaryotes, the DNA coding for a protein is not stored continuously, but as multiple coding sequences (exons) interspersed with noncoding introns. A variety of proteins may be generated from the same base sequence by selectively including or omitting exons or introns.
$\begin{figure} \begin{center} \includegraphics[scale=0.4]{figures/splicing} \end{center} \end{figure}$

Translation

Once in the cytoplasm, mRNA molecules bind to another large molecule called a ribosome. A ribosome reads an mRNA molecule in triplet known as codons. Each codon maps to one of twenty possible amino acids, that are chained together in the order specified by the mRNA. The newly created amino acid chain then folds into a complex three-dimensional protein structure.

Whereas DNA is a stable molecule, mRNA and proteins have only limited lifespan before they are broken down and their constituent nucleotides and amino acids are reused. Both mRNA and proteins may be degraded at different rates depending on their conformation and the presence or absence of other chemicals in the cell. While the most well understood form of regulation occurs at the transcriptional level, control of gene expression may be exercised at the at almost any stage of protein synthesis. Regulation is also known to occur at the level of RNA processing, mRNA transport and translation, protein modification and mRNA and protein degradation.

Next: The control tasks of Up: Biological background Previous: Biological background

Nic Geard 2004-05-06