Introduction to Bioinformatics II Lecture 5 By Ms. Shumaila Azam.

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Presentation transcript:

Introduction to Bioinformatics II Lecture 5 By Ms. Shumaila Azam

Exons And Introns Genes comprise only about 2% of the human genome. The rest consists of non-coding regions –chromosomal structural integrity, –cell division (e.g. centromere) –regulatory regions: regulating when, where, and in what quantity proteins are made. The terms exon and intron refer to coding (translated into a protein) and non-coding DNA, respectively.

Exons exons are the parts of the gene that will represent the codons for creating the protein Exons are parts of DNA that are converted into mature messenger RNA (mRNA)DNARNA

Introns Introns lie between exons,and act as wasteful DNA, as they are cut out before the gene is translated (turned into a protein) Introns are parts of genes that do not directly code for proteins. Introns are commonly found in multicellular eukaryotes, such as humans. They are less common in unicellular eukaryotes, such as yeast, and even rarer in bacteria. It has been suggested that the number of introns an organism’s genes contains is positively related to its complexity. That is the more introns an organism contains, the more complex the organism is.

How introns are removed? Introns are present in the initial RNA transcript, known as pre-mRNA. They need to be removed in order for the mRNA to be able to direct the production of proteins. Pre-mRNA, therefore, undergoes a process, known as splicing, to create mature mRNA. It is vital for the introns to be removed precisely, as any left-over intron nucleotides, or deletion of exon nucleotides, may result in a faulty protein being produced.

How introns are removed? This is because the amino acids that make up proteins are joined together based on codons, which consist of three nucleotides. An imprecise intron removal thus may result in a framshift, which means that the genetic code would be read incorrectly. E.g BOB THE BIG TAN CAT wrong intron removal can cause OBT HEB IGT ANC AT…

RNA Splicing RNA splicing, also known as RNA processing, occurs at special splice sites. These tend to begin with the dinucleotide GU at the 5’ end and AG at the 3’ end. The process is carried out by small nuclear ribonucleo proteins (snRNPs), which are commonly known as snurps. They bind to both the 5’ and 3’ ends of the intron and cause the intron to form a loop. The intron is then removed from the sequence and the two remaining exons are linked together.

RNA Splicing

Altrnative Splicing Alternative splicing refers to the way that different combinations of exons can be joined together. This idea was first put forward by Walter Gilbert. He proposed that the different permutations of exons could produce different protein isoforms. These in turn would have different chemical and biological activities.

Alternative Splicing There are more than 1,000,000 different human antibodies. Alternative splicing refers to the different ways of combining a gene’s exons. This can produce different forms of a protein for the same gene. Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in higher eukaryotes. E.g. It is now thought that between 30 and 60% of human genes undergo alternative splicing.

Altrnative Splicing Moreover, it is said that many human diseases may be connected to problems with splicing. Example: – One example of a human gene that undergoes alternative splicing is fibronectin. Over 20 different isoforms of fibronectin have been discovered. These have all been produced from different combinations of fibronectin gene exons.

Alternative Splicing

Immunoglobulin B cells produce antibody molecules called immunoglobulin (Ig) which fall in five broad classes. Diversity of Ig molecules –DNA sequence: recombination, mutation. –mRNA sequence: alternative splicing. –Protein structure: post-translational proteolysis, glycosylation.

Splicing.html Splicing.html

Translation Ribosome: –cellular factory responsible for protein synthesis; –a large subunit and a small subunit; –structural RNA and about 80 different proteins.

Translation transfer RNA (tRNA): –adaptor molecule, between mRNA and protein; –specific anti-codon and acceptor site; –specific charger protein, can only bind to that particular tRNA and attach the correct amino acid to the acceptor site.

Translation Initiation –Start codon AUG, which codes for methionine, Met. –Not every protein necessarily starts with methionine. Often this first amino acid will be removed in post-translational processing of the protein. Termination: –stop codon (UAA, UAG, UGA), –ribosome breaks into its large and small subunits, releasing the new protein and the mRNA.

Translation

translation-basic.html translation-basic.html

Post-translational processing Folding. Cleavage by a proteolytic (protein-cutting) enzyme. Alteration of amino acid residues –phosphorylation, e.g. of a tyrosine residue. –glycosylation, carbohydrates covalently attached to asparagine residue. –methylation, e.g. of arginine. Lipid conjugation.

Control of Gene Expression there is strong evidence that the DNA content of most cells in a multi-cell organism is identical different cell types synthesize different sets of proteins at different times

Control of Gene Expression there are at least six ways to control protein expression 1.control when and how often a gene is transcribed 2.control how the transcript is spliced 3.select which mRNA's are exported from the nucleus 4.control translation

Controlling Expression 5.selectively destabilize mRNAs in the cytoplasm 6.control protein activity (degradation, inactivate, isolate), post-translational modifications for most genes transcriptional control is the most important for many diseases specific patterns of gene expression (mRNA expression) have been associated with the different phenotypes