After transcription, the RNA must be processed before it can be translated. As described elsewhere, RNA processing involves addition of a 5' cap, addition of a 3' poly (A) tail, and removal of introns. This processing represents another level of regulation of gene expression, particularly in regard to splicing out of introns. Regulation can be of two types: a) whether an RNA gets processed; and b) which exons are retained in the mRNA.
The first type of regulation can determine whether or not an mRNA gets translated. If an RNA is not processed, it will not be transported out of the nucleus, and will not be translated.
The second type of regulation can affect the function of the protein produced. Some genes have exons that can be exchanged in a process known as exon shuffling. For example, a gene with four exons might be spliced differently in two different cell types. In cell 1, exons 1, 2, and 4 would be used in the mRNA:
In cell 2 on the other hand, exons 1, 3, and 4 would be used:
In each of these cases, the polypeptide produced could have a different function. In mammals, for example, the calcitonin gene produces a hormone in one cell type, and a neurotransmitter in another cell type, due to exon shuffling. In Drosophila, alternate splicing of the sex-lethal RNA can produce an mRNA encoding a functional polypeptide, or one with a premature stop codon that encodes a short, nonfunctional polypeptide.
Regulation of RNA Longevity
Imagine two mRNA molecules: one lasts for five minutes in the cytoplasm before being degraded, while the other one manages to linger for an hour before being degraded. If both are translated continually while they exist, it is obvious that more of the second polypeptide will be produced than the first. This is the principle behind regulation of RNA longevity. mRNAs from different genes have their approximate lifespan encoded in them; this serves to help regulate how much of each polypeptide is produced. The information for lifespan is found in the 3' UTR. The sequence AUUUA, when found in the 3' UTR, is a signal for early degradation (and therefore short lifetime). The more times the sequence is present, the shorter the lifespan of the mRNA. Because it is encoded in the nucleotide sequence, this is a set property of each different mRNA; the longevity of an mRNA can't be varied.
Regulation of Translation
Whether or not an mRNA molecule is translated can be regulated as well. The various mechanisms of translational regulation are incompletely understood, but there are many documented examples (particularly in embryonic development) of mRNA molecules that are present routinely, but are only translated under certain circumstances. For example, many animals sequester large amounts of mRNA in their eggs, and those mRNA molecules are not translated unless the egg is fertilized.
Whether or not a gene is transcribed is the major way that gene expression is regulated in eukaryotes, as it was in prokaryotes. There are some major differences between transcriptional regulation in prokaryotes and eukaryotes. For one thing, because of the complexity of eukaryotic patterns of gene expression, each eukaryotic gene needs its own promoter. In other words, eukaryotic genes are not organized into operons. Another difference is that prokaryotic genes are regulated primarily by repressors. Although repressors occasionally play a role in eukaryotes, eukaryotic genes are primarily regulated by transcriptional activators. These activators are transcription factors.
Regulatory Elements of Eukaryotic Genes
As discussed in the module on transcription, eukaryotic genes have promoters that are recognized by basal transcription factors (such as TFIID). In addition to the promoter, eukaryotic genes have one or more enhancers. These are DNA sequences associated with the gene being regulated, and whereas the promoter is responsible for initiating low levels of transcription and determining the transcription start site, enhancers are responsible for increasing ("enhancing") transcription levels, and they are responsible for regulating cell- or tissue-specific transcription (i.e. the transcription responsible for differentiation). There are some other basic differences between enhancers and promoters, which are outlined in the module on transcription.
Enhancers function by being recognized and bound to by transcription factors. These are not the basal-type transcription factors (such as TFIID) discussed elsewhere. These are specialized transcription factors, of which there are very many types (all are proteins). A very large number of enhancer elements has been identified and characterized, and each different enhancer has its own transcription factor that it binds to.