mRNA) that is then translated into protein. Each of these steps is controlled by specific sequence elements, or regions, within the gene. Every gene, therefore, requires multiple sequence elements to be functional.[2] This includes the sequence that actually encodes the functional protein or ncRNA, as well as multiple regulatory sequence regions. These regions may be as short as a few base pairs
The structures of both eukaryotic and prokaryotic genes involve several nested sequence elements. Each element has a specific function in the multi-step process of
mRNA or non-coding RNA. This 'sense' or 'coding' strand, runs in the 5' to 3' direction where the numbers refer to the carbon atoms of the backbone's ribose sugar. The open reading frame (ORF) of a gene is therefore usually represented as an arrow indicating the direction in which the sense strand is read.[7]
repressor proteins.[11][12] Enhancers and silencers may be distantly located from the gene, many thousands of base pairs away. The binding of different transcription factors, therefore, regulates the rate of transcription initiation at different times and in different cells.[13]
Regulatory elements can overlap one another, with a section of DNA able to interact with many competing activators and repressors as well as RNA polymerase. For example, some repressor proteins can bind to the core promoter to prevent polymerase binding.[14] For genes with multiple regulatory sequences, the rate of transcription is the product of all of the elements combined.[15] Binding of activators and repressors to multiple regulatory sequences has a cooperative effect on transcription initiation.[16]
Although all organisms use both transcriptional activators and repressors, eukaryotic genes are said to be 'default off', whereas prokaryotic genes are 'default on'.[5] The core promoter of eukaryotic genes typically requires additional activation by promoter elements for expression to occur. The core promoter of prokaryotic genes, conversely, is sufficient for strong expression and is regulated by repressors.[5]
3' untranslated regions (blue) regulate translation into the final protein product.[17]
An additional layer of regulation occurs for protein coding genes after the mRNA has been processed to prepare it for translation to protein. Only the region between the
protein-coding region into a string of amino acids that fold to form the final protein product. In the case of genes for non-coding RNAs, the RNA is not translated but instead folds to be directly functional.[20][21]
Eukaryotes
The structure of eukaryotic genes includes features not found in prokaryotes. Most of these relate to
mature mRNA ready for translation into protein. Eukaryotic genes typically have more regulatory elements to control gene expression compared to prokaryotes.[5] This is particularly true in multicellular eukaryotes, humans for example, where gene expression varies widely among different tissues.[11]
A key feature of the structure of eukaryotic genes is that their transcripts are typically subdivided into
mature mRNA molecule, while intron regions are spliced out (excised) during post-transcriptional processing.[22] Indeed, the intron regions of a gene can be considerably longer than the exon regions. Once spliced together, the exons form a single continuous protein-coding regions, and the splice boundaries are not detectable. Eukaryotic post-transcriptional processing also adds a 5' cap to the start of the mRNA and a poly-adenosine tail to the end of the mRNA. These additions stabilise the mRNA and direct its transport from the nucleus to the cytoplasm, although neither of these features are directly encoded in the structure of a gene.[18]
The overall organisation of prokaryotic genes is markedly different from that of the eukaryotes. The most obvious difference is that prokaryotic ORFs are often grouped into a
ribosome binding site (RBS) so that ribosomes simultaneously translate ORFs on the same mRNA. Some operons also display translational coupling, where the translation rates of multiple ORFs within an operon are linked.[25] This can occur when the ribosome remains attached at the end of an ORF and simply translocates along to the next without the need for a new RBS.[26] Translational coupling is also observed when translation of an ORF affects the accessibility of the next RBS through changes in RNA secondary structure.[27] Having multiple ORFs on a single mRNA is only possible in prokaryotes because their transcription and translation take place at the same time and in the same subcellular location.[23][28]
The
operator sequence next to the promoter is the main regulatory element in prokaryotes. Repressor proteins bound to the operator sequence physically obstructs the RNA polymerase enzyme, preventing transcription.[29][30]Riboswitches are another important regulatory sequence commonly present in prokaryotic UTRs. These sequences switch between alternative secondary structures in the RNA depending on the concentration of key metabolites. The secondary structures then either block or reveal important sequence regions such as RBSs. Introns are extremely rare in prokaryotes and therefore do not play a significant role in prokaryotic gene regulation.[31]