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Lecture 5 translation and protein synthesis-dr faisal al-allaf

Lecture 5 translation and protein synthesis-dr faisal al-allaf






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    Lecture 5 translation and protein synthesis-dr faisal al-allaf Lecture 5 translation and protein synthesis-dr faisal al-allaf Presentation Transcript

    • Dr. Faisal Al-Allaf Assistant Professor of Genetics and Molecular Medicine Umm Al-Qura University Faculty of Medicine, Makkah, Saudi Arabia fallaf@uqu.edu.sa Tel/Fax: 5270000 Ext: 4198 The Cellular and Molecular Basis of Inheritance1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 1
    • ‫ﻟﺘﺴﻬﻴﻞ ﻓﻬﻢ اﻟﻤﺤﺘﻮى اﻟﻌﻠﻤﻲ واﻟﺤﺼﻮل ﻋﻠﻰ آﺎﻣﻞ اﻟﺪروس ﻟﻬﺬا اﻟﻤﻘﺮر‬‫ﻓﺴﻴﺘﻢ ﺗﻔﻌﻴﻞ اﻟﺘﻌﻠﻴﻢ اﻹﻟﻜﺘﺮوﻧﻲ ﻋﻦ ﺑﻌﺪ. ﺳﻴﺘﻴﺢ ﻟﻚ اﻟﺘﻌﻠﻴﻢ اﻹﻟﻜﺘﺮوﻧﻲ ﻓﺮﺻﺔ‬‫إﺟﺮاء اﻹﻣﺘﺤﺎﻧﺎت واﻟﻤﺬاآﺮة واﻹﺳﺘﺮﺟﺎع ﻣﻦ اﻟﺒﻴﺖ. آﻤﺎ ﺳﻴﻤﻜﻨﻚ ﻣﻦ‬‫اﻟﺤﺼﻮل ﻋﻠﻰ اﻟﻨﺴﺦ اﻻﻟﻴﻜﺘﺮوﻧﻴﺔ ﻟﻠﺪروس. ﺑﺈﻣﻜﺎﻧﻨﺎ أﻳﻀﺎ إﺟﺮاء اﻟﺤﻮارات‬ ‫ﺣﻮل ﻣﻮاﺿﻴﻊ اﻟﻤﻘﺮر وﺑﺈﻃﻼع اﻟﺠﻤﻴﻊ.‬ ‫ﻟﺘﻔﻌﻴﻞ ﺗﺴﺠﻴﻠﻚ ﻓﻲ اﻟﺘﻌﻠﻴﻢ اﻹﻟﻴﻜﺘﺮوﻧﻲ ﻋﻦ ﺑﻌﺪ ، ﻧﺮﺟﻮ زﻳﺎرة اﻟﺮاﺑﻂ:‬‫‪http://el.uqu.edu.sa/jusur/index.php?un_id=uqu‬‬ ‫ﻟﻺﻃﻼع ﻋﻠﻰ اﻟﻤﻌﻠﻮﻣﺎت اﻟﺨﺎﺻﺔ ﺑﺄﺳﺘﺎذ هﺬا اﻟﻤﻘﺮر وﻣﻌﺮﻓﺔ اﻟﺴﺎﻋﺎت‬ ‫اﻟﻤﻜﺘﺒﻴﺔ ﻟﻠﺘﻮاﺻﻞ ﻣﻌﻪ ، ﻧﺮﺟﻮ زﻳﺎرة اﻟﺮاﺑﻂ:‬‫‪http://www.uqu.edu.sa/faallaf‬‬ ‫12/40/1341‬ ‫‪Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa‬‬ ‫2‬
    • Course contents (syllabus)GENOME, TRANSCRIPTOME, AND PROTEOME Cell, DNA and RNA Gene structure and genetic codes Cell cycle and DNA replication Transcription and post-transcriptional modification RNA and regulation of gene expression Translation and post-translational modificationCHROMOSOMES AND CELL DIVISION Chromosomes morphology and classification Cell cycle division Mitosis Meiosis1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 3
    • Flow of genetic information:the central dogma The process of the transfer of the genetic information from DNA to RNA to protein has been called the central dogma DNA can be replicated to give DNA RNA can be converted into DNA by retroviruses only Proteins cannot be converted into RNA or DNA At the end of transcription, mRNA is transported from the nucleus to the cytoplasm where it attached to the ribosomes. The genetic information coded in the mRNA transcript will then be translated into polypeptide. Thus, Translation is the transmission of the genetic information from mRNA to protein ReplicationDNA RNA Proteins Transcription Translation1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 4
    • Endoplasmic reticulum (ER) There are two types of ER- Rough Endoplasmic Reticulum (RER) Smooth Endoplasmic Reticulum (SER) The membrane of RER have ribosomes attached to them and they are specialized in the synthesis and secretion of proteins The SER is devoid of ribosome. The SER is responsible for the synthesis of cholesterol and phospholipids and it is prominent in cells that are active in lipid biosynthesis.1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 5
    • Function of ribosomes Translation of genetic information encoded in the mRNA transcript occur in the ribosomes In eukaryotic cell, each ribosome consists of two unequal subunites, Small subunit (S) Large subunit (L) Ribosome is vital in translation. It holds mRNA transcript and tRNA together, ensuring accuracy of protein synthesis and correct orientation of amino acids synthesis. Amino acids are linked together by formation of a peptide bond1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 6
    • The genetic code provides a dictionary fortranslation of mRNA transcript Messenger RNA is translated from the 5’ to 3’ end within cytoplasmic ribosomes. The resultant polypeptides are then modified into proteins Each amino acid is represented in mRNA by one or more groups of three bases called codons and their interpretation as a polypeptide is called translation Protein is the main structural components of the body. Protein can also be a hormone or enzyme Each protein derived from one or more polypeptides. A polypeptide is a chain of amino acids. Its sequence is determined by that of the bases in the corresponding mRNA, in accordance with the genetic code The functional properties of proteins derived largely from the active groups they display in their tertiary and quaternary conformation1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 7
    • Translation and protein synthesis Translation is the mRNA-directed biosynthesis of polypeptide. Translation occurs in three sequential phases: Initiation Elongation Termination The components needed for translation are mRNA, tRNA, ribosome, GTP, initiation factors, elongation factors, and release factors A. As combine with their corresponding tRNA, this incorporates a high-energy ester bond between the aminoacyl group and the 3’ CCA group of the tRNA. This incorporation is known as charging of the tRNA1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 8
    • tRNA and translation Translation requires tRNA molecule charged with amino acid (A.A.) appropriates to their anticodon sequences. Thus, tRNA acts as an adaptor molecule No direct pairing between mRNA and amino acids No direct pairing between DNA and amino acids In the ribosomes the mRNA forms the template for producing the specific sequence of amino acids of a particular polypepetide1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 9
    • Translation initiation A small ribosomal subunit containing several initiation factors and methionyl tRNA charged with methionine binds to the 5’ cap on the mRNA, then slid along until it finds and engages with the first AUG start sequence on mRNA Each mRNA contains many AUG start codons in its various reading frames. The one corresponding to the start of translation is preceded by a purine-rich tract of nucleotides called Shine-Dalgrano sequence. This binds to a corresponding pyrimidine-rich sequence in the ribosomal S unit The start codon determines the reading frame and the amino terminal end of the polypeptide1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 10
    • Translation initiation The initiation factors are released, a large ribosomal subunit binds to the small one and translation then begins The large ribosoaml subunit contains two sites known as the aminoacyl (A) site and the peptidyl (P) site At the end of initiation stage, the P site contains a charged met-tRNA with its anticodon engaged in the first AUG codon, while the A site is empty1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 11
    • Chain elongation Chain elongation involves the addition of aminoacyl residues to the growing polypeptide. It is a three stage process: Stage one: Aminoacyl-tRNA binds to the ribosomal A site. In this stage, a complex of aminoacyl-tRNA, GTP, and elongation factor is formed Stage two: peptidyl group in the P site is added onto the aminoacyl group in the A site Stage three: the translocation process occurs1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 12
    • Termination of translation The UAA, UGA and UAG are not recognised by tRNAs, and these are termed termination or stop codon. These codons mark the end of a polypeptide and signal to ribosome to stop synthesis The termination codons, UAA, UAG, and UGA are recognised by Release Factors (RFs) rather than tRNA The binding of an RF causes the peptidyl transferase to transfer the peptidyl group to water rather than to aminoacyl group. The uncharged tRNA is released from the ribosome and the RFs are expelled.1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 13
    • Post-translation modification Translation is not the end of the genome expression pathway. The polypeptide that emerges from the ribosome is inactive and before taking on its functional role in the cell must undergo at least one of the following four types of post-translational modification Protein folding Peptide cleavage by proteolytic enzymes Chemical modification in ER lumen or the Golgi apparatus Intein splicing1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 14
    • Protein folding The polypeptide is usually inactive until it is folded into its correct tertiary structure1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 15
    • Polypeptide cleavage Enzymes known as proteases may cut and remove segments from one or both ends of the polypeptide, resulting in a short ended form of the protein They may also cut the polypeptide into a number of different segments, or some of which are active1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 16
    • Polypeptide cleavage Signal peptide or leader sequence is a conserve hydrophobic amino acid sequence of 18-30 A.A. residues near the amino terminus of the polypeptides that directs non-cytoplasmic polypeptides into the ER lumen as they are translated1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 17
    • Chemical modification Individual A.A in the polypeptide might be modified by attachment of new chemical group. Chemical modifications occur in the ER lumen or the Golgi apparatus and including: Glycosylation involved addition of oligosacharide to specific A.A. residue Phosphorylation involved addition of phosphate group and targets Ser or Tyr residues Sulphation involved addition of sulphate group and targets Tyr residue. It is important for compartmentalization and biological activity Lipidation of Cys and Gly residue, which is necessary for anchoring proteins into the membrane Acetylation of Lys which can change the charge of the residue Hydroxylation which targets Lys and Pro residues. It is important in the production of collagen and extracellular matrix protein1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 18
    • Intein splicing Inteins are intervening sequences in some proteins, similar in a way to introns in mRNA. They have to be removed and the exteins ligated in order for the protein to become active1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 19
    • Control of gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA The level of expression of housekeeping genes are fixed irrespective of changes in the cell environment The level of expression of inducible/repressible genes are altered by cellular environment In addition to epigenetic control (eg: histone modification, DNA methylation), there are six other control points of gene expression at the level of transcriptional and translation1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 20
    • 1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 21
    • 1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 22
    • References and Private Reading These slides are only a handout and the students must read the text book (Emery’s element of medical genetics)1. Emery’s Elements of Medical Genetics, 13th edition 2007, by Peter TURNPENNY and Sian ELLARD. Churchill Livingstone ELSEVIER. ISBN: 978-0-7020-2917-22. Medical Genetics at a Glance, 2nd edition 2008, by Dorian PRITCHARD and Bruce KORF. Blackwell Publishing. ISBN: 978-1-4051-4846-73. Genetics for Dummies, 2005, by Tara Robinson, Wiley Publishing, Inc. ISBN: 978- 0-7645-9554-74. Cell Biology and Genetics, Crash Course, 2nd edition 2006, by Manson, Jones, Morris, Michael STEEL and Dan HORTON-SZAR. MOSBY ELSEVIER. ISBN: 0- 7234-3248-15. Human Molecular Genetics, 3rd edition, 2003, by STRACHAN T. and A. READ. Garland science/Taylor and Francis group. ISBN: 978-0-8153-4182-66. Genomes, 3rd edition 2006, by T.A. BROWN. Garland science, ISBN: 978-0-8153- 4138-31431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 23
    • Acknowledgments For the providers of all the educational materials (video clips, pictures, diagrams and charts) including publishers, pharmaceutical companies or unknown internet users who made their material available for use, in this and other presentations, I offer heartfelt thanks and deep appreciation. I feel particularly grateful to faculty, staff, and our brilliant students who provided a unique intellectual and wonderful environment for work.1431/04/21 Dr. Faisal Al-Allaf, fallaf@uqu.edu.sa 24