Proteins, Mutations and Genetic Disorders

What you should know One gene, many proteins as a result of 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.

One Gene, Many proteins… Recent studies about the human genome have revealed that there are about 21,000 protein-coding genes In the human body, the number of proteins are in excess of 25,000, and earlier estimates were that the human genome would comprise 100,000 genes In fact, only about 1.5% of the genome represents protein- coding genes, the rest being associated with non-coding RNA one gene must be able to encode many proteins, i.e. a variety of proteins can be expressed by the same gene This is achieved by two processes: alternative RNA splicing and post-translational modification (PTM)

The coding sections of a gene (the exons) can be split into several sections by non-coding sections (the introns) The name 'exon' is short for 'expressed region'; 'intron' is perhaps best remembered as the 'in- between' sections Particular exons can either be included or excluded from the mature transcript. It is also possible that two splice sites are produced at one end of an exon, making it possible to produce multiple transcripts by 'alternative splicing‘ Alternative RNA Splicing

In humans, it is estimated that alternative splicing occurs in more than 60% of genes In the example in the diagram below, when the introns are removed, exons 1 and 2 may either be spliced with exon 3 or with exon 4

Alternative splicing

Post-translational modification Once translation is complete, further modification may be required to enable a protein to perform its specific function Defects in PTMs have been linked to numerous developmental disorders and human diseases

Cleavage a protease enzyme cuts (cleaves) one or more bonds in a target protein to modify its activity This processing may lead to activation, inhibition or destruction of the protein's activity The protease may remove a peptide segment from either end of the target protein it may also cleave internal bonds in the protein that lead to major changes in the structure and function of the protein

Insulin and post-translational modification See figure 3.14 on pg 42 of TB Insulin starts as a single polypeptide chain To become active it requires its central section to be cut out by protease enzymes This results in in two polypeptide chains held together by sulphur bridges

Modification by the addition of a phosphate Phosphorylation is one of the most intensely studied post–translational modifications This PTM plays critical roles in the regulation of many cellular processes including: cell cycle, growth, apoptosis and differentiation.

Phosphorylation of p53 Regulatory protein p53 (normally inactive) requires the addition of a phosphate by phosphorylation to become activated in order to repair DNA

Mucus adheres to many epithelial surfaces, where it serves as a diffusion barrier against contact with noxious substances and as a lubricant Mucus is a glycoprotein consisting of protein and an added carbohydrate Modification by the addition of a carbohydrate

Do you know ? One gene, many proteins as a result of 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.