| << Chapter < Page | Chapter >> Page > |
After the initial pre-mRNA transcript has been created the first major modification is the addition of a 5' methyl guanosine cap. The addition of the 5' 7-MG cap is important for two reasons: the 5' caps are recognized by protein factors that initiate translation, and it also helps protect the transcript from nucleases. Nucleases are very common in the cell and because of this unprotected RNA has a very short half-life inside the cell. Nucleases are actually so common that working with RNA in the laboratory can be quite difficult because the samples have a tendency to disintegrate into useless bits.
Eukaryotic genes contain two types of transcribed regions: introns and exons. Exons are the regions of the genome that contain actual coding information. Introns are non-coding, meaning that intronic sequences are never translated to protein. Introns are never included in the final processed mRNA transcript. Splicing is the process of removing introns from the pre-mRNA transcript to produce an exon-only mRNA molecule, which is then shipped off for translation. Generally, eukaryotic mRNAs are considered to monogenic. Monogenic means that an RNA transcript contains exons from only one gene. However, up to one fourth of the transcripts in C. elegans have been show to be multi-genic (i.e. they contain exons from multiple genes).
A further complication of the splicing process is that mRNA can undergo alternative splicing. To illustrate this let's imagine a gene that has 3 exons and two introns. From this gene, three different final transcripts are possible. In all transcripts the two introns are going to be removed, but the cell can combine the exons however it wants as long as the original order is maintained. This means that for this example the possible mRNA transcripts include: Exon1-Exon2, Exon1-Exon3, and Exon1-Exon2-Exon3; however, Exon3-Exon1 is not possible because the exons are out of order.
An interesting side note is that some introns are capable of self-splicing, that is they can politely remove themselves without the intervention of any proteins. This is significant mainly because it is a significant counter example to the idea that RNA is an inert transcript and action is soley the domain of proteins. RNAs should really be viewed as having both enzymatic properties and abstract information-carrying ability. Because of this many people believe that RNA was the original genetic molecule and that DNA and proteins evolved later in the game.
Alternative splicing is a very important and powerful tool. To understand the benefit alternative splicing gives the cell we need to understand something about proteins. Proteins can be understood as containing modularized functional units. These functional units can be active sites on enzymes, large structural motifs such as beta-sheets or alpha-helices, or motifs that direct the eventual destination of expressed proteins. A good example of an alternatively spliced pre-mRNA transcript is the mouse IgM immuoglobulin transcript. IgM exists in two forms: excreted and membrane bound. These two forms of the protein differ in the only in the C-terminus: the secreted protein has a secreted terminus motif while the membrane-bound protein has a C-terminal membrane anchor region. Both products come from the same pre-mRNA, but alternative splicing includes either the terminal exon that creates the excreted form of IgM or the membrane-bound form of IgM.
The poly(A) tails are formed in a two step process: an endonulcease cleaves around 1000-2000 non-coding bases from the 3' end of the pre-mRNA transcript and then poly(A) polymerase adds 20-200 AMP molecules to the 3' end of the transcript. The poly(A) tail is important in the cellular transport of the mRNA transcript and, like the 5' cap, also helps to stabilize the mRNA transcript.
Notification Switch
Would you like to follow the 'Statistical machine learning for computational biology' conversation and receive update notifications?
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|