proteins, mutations and genetic disorders. what you should know one gene, many proteins as a result...
TRANSCRIPT
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Proteins, Mutations and Genetic Disorders
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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.
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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)
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• 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
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• 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
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Alternative splicing
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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
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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
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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
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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.
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Phosphorylation of p53
• Regulatory protein p53 (normally inactive) requires the addition of a phosphate by phosphorylation to become activated in order to repair DNA
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• 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
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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.