(e) Different proteins can be expressed from one gene as a result of alternative RNA splicing and post-translational modification. Different mRNA molecules are produced from the same primary transcript depending on which RNA segments are treated as exons and introns.
Post translation protein structure modification by cutting and combining polypeptide chains or by adding phosphate or carbohydrate groups to the protein.
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Homework Sheets 1_5/ 1_5A, 1_5B
source: RNA Splicing: Introns, Exons and Spliceosome By: Suzanne Clancy, Ph.D. © 2008 Nature Education
It is now becoming clear that the number of genes present in cells is fewer than the number of proteins which those cells can produce. This is as a result of some genes being capable of producing more than one protein product. There are two processes which contribute to the production of more than one protein. Post transcriptional processes (alternative RNA splicing) and post translational modification.
Alternative RNA splicing
For most eukaryotic genes (and some prokaryotic ones), the initial RNA that is transcribed from a gene’s DNA template must be processed before it becomes a mature messenger RNA (mRNA) that can direct the synthesis of protein. In this way, the primary mRNA transcript becomes the mature mRNA transcript. This process is known as splicing.
RNA splicing involves the removal or “splicing out” of certain sequences in the mRNA, referred to as intervening sequences, or introns. The final or mature mRNA thus consists of the remaining sequences, called exons, which are connected to one another during the splicing process.
Splicing different combinations of exon together can lead to the production of a variety of different proteins being produced from a single gene. In the diagram below, three different proteins have been produced from the same gene, as a result of combining different exons together.
Examples of genes where alternative splicing leads to the production of different protein products include the gene CGRP (Calcitonin Gene Related Peptide), which can produce either CGRP or calcitonin depending on what splicing activity occurs. Typically CGRP, a neurotransmitter, is the product found in neurones and calcitonin, a hormone conerned with regulation of calcium levels in the blood is produced in non-neuronal cells such as the thyroid gland.
Post Translational Processing
In addition to differences between the mRNA transcripts exported to the ribosome, the protein produced by the ribosome can become modified following synthesis. Modifications can include proteolytic cleavage (enzymes break the protein into smaller, functional fragments), or the addition of various other molecules including sugars (known as glycosylation) or phosphate groups (phosphorylation).
Cleavage
The gene known as the POMC (pro-opio melanocortin) gene encodes a 285-amino acid polypeptide hormone precursor that is processed by enzymatic cleavage to produce a range of protein products. The protein produced is tissue specific and each has a different function within the body including roles in pain, regulating metabolic rate, pigmentation and immune function.
Glycosylation
A number of proteins including mucus and cell – cell adhesion moleules and cell-cell recognition molecules are glycosylated after synthesis. Glycosylation is required for the correct functioning of these molecules, and a number of conditions, occurring as a result of disorders of glycosylation have been identified.
Phosphorylation
Regulation of proteins by phosphorylation is a very common method of regulation of cell function. the protein switches between a phosphorylated and an unphosphorylated form, and one of which is active, the other one inactive. The phosphates groups are added and removed by enzymes (kinase and phosphatases respectiviely). The importance of phosphorylation is illustrated by p53, a tumour suppressor protein which stops cell division. A number of cell changes, including DNA damage cause the protein to become phopshorylated, which causes it to become active. Active p53 protein then instructs the cell to respone appropriately to the damge intis DNA, this could be repairing the damage of even causing programmed cell death (apopotosis).
For some people, the gene encoding p53 can become damaged by mutation or they can inherit a faulty version. In such cases, p53 protein is inactive and these individuals are more likely to develop some types of cancer. The human papilloma virus, associated with the development of cervical cancer produces a protein which inactivates p53.
