Cells and Molecules
Cells and Molecules BS 111
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Helen Blick Sr.
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Helen Blick Sr.
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This 47 page Class Notes was uploaded by Helen Blick Sr. on Saturday September 19, 2015. The Class Notes belongs to BS 111 at Michigan State University taught by Richard Allison in Fall. Since its upload, it has received 41 views. For similar materials see /class/207330/bs-111-michigan-state-university in Biological Sciences at Michigan State University.
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Date Created: 09/19/15
Chapter 11 Cell Signaling 111 External signals are converted to responses within the cell 0 Evolution of Cell Signaling 0 Yeast mate with quotaquot signaling to bind to receptor proteins of quotatquot which signals for a chemical to bond to receptors on quotaquot cells without actually entering I Exchange ofmating factors I Mating binding of factors to receptors I New aoc cell fused nucleus includes genes of aoc 0 Signal transduction pathway process by which a signal on a cell s surface is converted to a specific cellular response in a series of steps 0 Local and LongDistance Signaling 0 Cell junctions animals and plant cells have celljunctions gaps that allow molecules to pass between adjacent cells without crossing plasma membranes gap junctions plasmodesmata o Cellcell recognition two cells in an animal communicate by interaction between molecules protruding from their surfaces 0 Growth Factors compounds that stimulate nearby target cells to grow and divide in animal cells 0 Local signaling I Paracrine signaling a secreting cell acts on nearby target cells by discharging molecules ofa local regulator ie a growth factor into the extracellular uid I Synaptic signaling a nerve cell releases neurotransmitter molecules into a synapse stimulating the target cell animal nervous system 0 Long distance signaling hormonalendocrine signaling endocrine cells secrete hormones into body uids blood which has potential to reach all body cells via the circulatory system 0 The Three Stages of Cell Signaling A Preview 0 Earl Sutherland 1971 Nobel Prize Reception target cell detection of signaling molecule quotdetectedquot once signaling molecule binds to a receptor protein inon the cell 2 Transduction a sequence of changes in a series ofquotrelay molecules Response transduced signal triggers a specific cellular response 112 Reception A signaling molecule binds to a receptor protein 0 Signaling cell behaves as a quotligand molecule which specifically binds to another molecule 0 Receptors in the Plasma Membrane 0 Water soluble signaling molecules bind to specific sites on receptor proteins embedded in the cell s plasma membrane 0 Intracellular Receptors 0 Proteins found in cytoplasm or nucleus of target cells 0 Transcription factors control which genes are turned on transcribed into mRNA into a particular cell at a particular time o Receptors 2quot o GProtein Coupled Receptors I Ribbonlike with 7 transmembrane oc helices loops form binding sites 0 Receptor Tyrosine Kinase I Kinase enzyme that catalyzes the transfer ofphosphate groups I Member receptors that attach phosphates to tyrosines 0 Ion Channel Receptors I Ligand gated ion channel gate opens or closes for ions like Na or Ca2 113 Transduction Cascades of molecular interactions relay signals from receptors to target molecules in the cell 0 Signal Transduction Pathways o Molecules relay signal from receptor to response at each step signal is transduced into a different form protein shape change which is brought out by phosphorylation 0 Protein Phosphorylation and Dephosphorylation 0 Protein kinase transfers phosphate groups from ATP to a protein 0 Protein phosphatases enzymes that rapidly remove phosphate groups from proteins dephosphorylation turns ofpathway 0 Small Molecules and Ions as Second Messengers 0 Small water soluble molecules readily spread throughout cell by diffusion o ie cyclic AMP and Ca2 0 Cyclic AMP 0 First messenger activates Gproteincoupled receptor activating a GProtein which activates adenylyl cyclase which catalyzes the conversion of ATP to camp The camp then acts as a second messenger and activates another protein kinase A leading to cellular responses 0 Calcium Ions and Inositol Phosphate 1P3 0 Animals muscle cell contraction secretion of substances cell division 0 Plants greening in response to light motility 114 Response Cell Signaling leads to regulation of transcription or cytoplasmic activities 0 Nuclear and Cytoplasmic Responses 0 Occurs in nucleus or cytoplasm o Signaling pathway activates a transcription factor that turns a gene on response is synthesis omeNA which will be translated into a specific protein 0 Fine Tuning of the Response 0 Signaling pathways amplify signal response and provide different points at which a cell s response can be regulated Signal Amplification at each catalytic step the number ofproducts increases 0 0 Specificity cells respond differently to the same signal due to different proteins 0 Signaling Efficiency scaffolding proteins large relay proteins permanently holding networks of signalingpathway proteins 0 Termination of the Signal when signaling molecules leave the receptor the receptor reverts to its inactive form 115 Apoptosis programmed cell death integrates multiple cellsignaling pathways 0 Cellular agents chop up DNA and fragment organellescytoplasmic components cell shrinks and becomes lobed quotblebbingquot o Apoptosis in the Soil Worm o Apoptosis is triggered by signals that activate a cascade of suicide proteins in the cells destined to die 0 Apoptosis and the Signals that Trigger Them 0 Apoptosis proteins form molecular pores in the mitochondrial outer membrane causing it to leak and release apoptosis proteins 0 Death signal Ced9 inactivated Ced3 protease triggers death reactions Cancer can be linked to failure of apoptosis melanoma due to faulty forms of C elegans Ced4 protein 0 Webbed feethandspaws caused by lack of apoptosis 0 Chapter 19 Viruses 191 A Virus consists of nucleic acid surrounded by a protein coat 0 The Discovery of Viruses o AdolfMeyer tobacco mosaic disease 0 Wendell Stanley crystallized TMV in 1935 0 Structure of Viruses o 20nm in diameter smaller than a ribosome 0 Infectious particles consisting of nucleic acid enclosed in a protein coat and sometimes a membranous envelope 0 Viral Genomes I Double or single stranded DNA or RNA 0 Capsids and Envelopes I Capsid protein shell enclosing viral genome rod helical viruses polyhedral icosohedral or complex shape Viral membranous envelopes contain host cell phospholipids and membrane proteins and proteinsglycoproteins ofviral origins I Bacteriophages phages most complex form ofa capsid I E Coli phage icosohedral head with protein tail piece with fibers which is how they attach to bacterium 192 Viruses reproduce only in host cells 0 Host range each type ofvirus can only affect a limited variety of hosts 0 General Features ofViral Reproductive Cycles 0 Virus enters cell and is uncoated releasing viral DNAcapsid proteins 0 Host enzymes replicate the viral genome 0 Host enzymes transcribe viral genome into viral RNA which host ribosomes use to make more capsid proteins 0 Viral genomes and capsid proteins selfassemble into new virus particles which eXit the cell 0 Reproductive Cycles of Phages o The Lytic Cycle kills the host cell I Bacterium lyses breaks open and releases phages produced within the cell Attachment entry and DNA degradation synthesis of virus assembly release Restriction enzymes quotrestrictquot the ability of the phage to infect the bacterium o The Lysagemic Cycle replication of the phage without killing I Turn host cell into phage producing quotfactoryquot I Phage attaches phage DNA integrated bacterium reproduces cell divisions produce large populations ofinfected bacteia I Diphtheria botulism and scarlet fever 0 Reproductive Cycles of Animal Viruses 0 Viral Envelopes I Glycoproteins bind on envelope bind to receptor molecules capsidviral genome enter cell viral genome templates synthesis of RNA copies of RNA are made RNA functions as mRNA vesicles transport envelope glycoproteins to the plasma membrane 0 RNA as Viral Genetic Material I Retroviruses RNA animal viruses with most complicated reproductive cycles armed with reverse transcriptase transcribes RNA template into DNA I ie HIVAIDS enters host cell and newly made viral DNA stays in the nucleus a quotprovirusquot and never leaves 0 Evolution ofViruses 0 Have a tremendous impact on all organisms due to disease causing ability 193 Viruses viroids and prions are formidable pathogens in animals and plants 0 Viral Diseases in Animals 0 Vaccine harmless variantderivative that stimulates immune system to mount defenses smallpox rubella mumps hepatitis B 0 Emerging Viruses o Suddenly appearingrecent West Nile in 1999 SARS 0 Viral Diseases in Plants 0 Bleachedbrown spots stunted growth damaged roots owers o TMV RNA genome helical capsid others have an icosohedral capsid 0 Horizontal transmission infected by external source insects o Viroids and Prions The Simplest Infectious Agents 0 Viroids I Circular RNA molecules I Infect plants I Cause abnormal development and stunted growth 0 Prions I Infectious proteins I Cause degenerative brain disease in animals I Incubate for 10 years before developing I No known cure I Misfolded form of protein converts nonfolded to folded I Proposed by Stanley Prusiner in 1980s 1997 Nobel Prize Chapter 20 Biotechnology 0 Technique used to form recombinant DNA segments ofDNA from 2 different sources 201 DNA cloning yields multiple copies ofa gene or other DNA segment 0 DNA Cloning and Its Applications 0 Isolate plasmids small circular DNA molecules and insert foreign DNA the plasmid is now a recombinant DNA molecule ie E Cali 0 Useful for resistance genes and proteins harvested in large quantities 0 Using Restriction Enzymes to Make Recombinant DNA 0 Restriction enzymes cut DNA 0 Restriction sites short DNA strands with sticky end 0 DNA ligase catalyzes formation 0 Cloning a Eukaryotic Gene 0 Original plasmid is quotcloning vector easily isolated and manipulated o Producing Clones of Cells Carrying Recombinant Plasmids o Isolate plasmid DNA from bacteria and DNA from bird 0 Cut both DNA samples with the same restriction enzyme 0 Mix the cut plasmids and DAN fragments 0 Mix the DNA with bacterial cells 0 Plate the bacteria on agar and incubate until colonies grow 0 Storing Cloned Genes in DNA Libraries 0 BAC bacterial artificial chromosome large plasmids trimmed down to ensure replication of 100300kb inserts o Complimentary DNA cDNA made from enzymatic degradation omeNA o Expressing Cloned Eukaryotic Genes 0 Bacterial Expression Systems I Expression vector promoter helps express foreign gene I Introns noncoding regions 0 Eukaryotic Cloning and Expression Systems I YACs yeast artificial chromosomes have essentials of eukaryotic chromosome origin for DNA replication centromere 2 telomers I Electroportation create holes in plasma membranes for DNA to enter 0 Amplifying DNA in Vitro The Polymerase Chain Reaction PCR 0 Quick and selective amplified specific DNA fragments fast 202 DNA technology allows us to study the sequence expression and function ofa gene 0 Gel Electrophoresis and Southern Blotting 0 GE molecular sieve negative charged DNA 0 SB GE with DNA transfer 0 DNA Sequencing o Dideoxy chain termination method Sanger allows to compare and contrast DNA from different species 0 Analyzing Gene Expression 0 Northern blotting 0 Reverse Transcriptase PCR cDNA synthesis PCR amplification Gel Electro Chapter 18 Regulation of Gene Expression 7 PH ENDOFLASMIC Wquot mcuLuu 15m h vuucLEuS mangn Nucleuid FluwllunL Hiboacmal Dmimsmn quot Plasma membrane quot I 39tholmu Puoxlnmo Cell wall 39 Bulgl appum Plum mmbmna Capsular I Micrownquot Micvomamms k Inma lmlnmlalzlllimms ax x 39 mummln Lysnsnml gmbm WW vQQ mmquot quot haclarlum Prokaryote and eukaryote compared Don t let the apparent structural simplicity of bacteria mislead you as bacteria are complex organisms alA Iyplcal rodIhaped Bacterial Genetics Prokaryotic organisms distinguish themselves from eukaryotes by their size and their lack of organelles Prokaryotic DNA is concentrated in a region referred to as the nucleoid but there is no membrane boundary separating the single chromosome from the cytosol We tend to acknowledge the presence of bacteria that interact with plants and animals but by far the majority of bacterial species remain undiscovered as we do not have the ability to culture them The best described species is Escherichia coli E coli This species makes up roughly 01 or our gut s bacterial flora E coli and other prokaryotic symbiotic inhabitants of our gut assist with the digestion of food an produce several required compounds including Vitamin K and Bcomplex vitamins Numerous strains of E coli existand some cause disease including human urinary tract Infections pneumonia meningitis traveler s diarrhea and food borne illnesses Controllinq Gene Expression in Prokarvotes E coli has over 4300 genes Many of these genes encode proteins with specific purposes and it is unnecessary to express all 4300 continuously For example E coli has the capacity to synthesize the amino acid Tryptophan If a bacterial cell can gather an adequate supply of the amino acid Trp from its environment then expressing the genes for Tryptophan biosynthetic pathway is a waste of energy and resources Therefore E coli has developed a method of monitoring the concentration of Trp in its environment and expresses the biosynthetic genes only when required Actually there are two methods of controlling Trp biosynthesis 1 Through feedback inhibition the presence of Trp inhibits the first enzyme in the biosynthetic pathway 2 Additionally Trp within the cell turns off the expression of the genes of the biosynthetic pathway by 3333 interacting with the promoter region and inhibiting Precursor l H trp ne I Enzyme 1 39 39 Regulation transcription C ofgene expression Enzyme 2 OI Enzyme 3 e i Tryptophan l a Regulation of enzyme b Regulation of enzyme actiVIty production Genes of Prokaryotes are packaged so that all the genes required for a process are expressed together This sensible packaging unit is called an Operon An operon consists of three elements 1 the genes ln bacteria the genes coding for the enzymes of a particular pathway are clustered together and transcribed as one long mRNA molecule 2 a promoter region where RNA polymerase binds 3 an operator region between the promoter and the first gene which acts as an onoff switch The operator provides a position on the chromosome where a physical barrier can be erected a protein which prohibits the RNA polymerase from proceeding to the genes The Tryptophan operon has 5 genes for Trp biosynthesis The operator provides a binding site for a repressor protein and the operator is located between the promoter and the Trp biosynthetic genes An additional gene trpR is upstream of the operon and expressed constitutiver all the time TrpR serves as a regulatory protein and monitors Trp concentration trp operon Promoter Promoter r Genes of operon DNAWM 4 trpE trpD trpC 1743 lb 7 T M Regulatory Operator gene 3 Start codon Stop codon mRNA RNA mRNA 539 polymerase i i l I 5 l l Protein Inactive Polypeptide subunits that make up repressor enzymes for tryptophan synthesis a Tryptophan absent repressor inactive operon on Couynghi 2m Pearson Emma c p b The repressor protein has the capacity to bind the amino acid Trp When Trp binds the repressor this allosteric protein changes shape and it can now bind the operator Binding inhibits the RNA polymerasepromoter interaction Promoter operator DNA J3941trpEtrpDtrpCtrpBtrpA No RNA made RNA Polymerase Protein Active repressor M Tryptaphan corepressor b Tryptophan present repressor active operon off The trp operon is an example of a repressible Oberon one that is inhibited when a specific small molecule binds allosterically to a regulatory protein In contrast an inducible operon is stimulated when a specific small molecule interacts with a regulatory protein ln inducible operons the regulatory protein is active inhibitory as synthesized and the operon is off Allosteric binding by an inducer molecule makes the regulatory protein inactive and the operon is on The Lac Operon is an Inducible Operon The disaccharide lactose is found in milk and must be broken down into monosaccharides glucose and galactose by Bgalactosidase for use as an energy source The uptake of lactose from the environment triggers the expression of the Bgalactosidase and two other genes involved in uptake and metabolism of lactose The key to lactose metabolism is the allosteric regulatory protein encoded by Lacl binds to the operator when lactose is not present The inducer allolactose is an isomer of lactose and is made from lactose entering the cell Allolactose binds the repressor and inhibits the repressor from binding to the operator thus clearing the way for RNA polymerase to bind and transcribe the operon Regulatory Promoter gene r Leakiness of this Operator MAW promoter N l 9 REM system allows 3 y made limited transcription quot RNA 5 FINA and thus small polymerase i quantltles of the Protein 333 protelns are present WIthIn the cell a Lactose absent repressor active operon off lac operon I I 7 a DNA W a an Iacz lacy l lt 1a 7 x L RNA quot 3 polymerase mRNA 5 mRNAs 39 i quot J Protein e jBGalactosidase I Permease Allolactose Inactive inducer repressor Transacetylase b Lactose present repressor inactive operon on 7 in Repressible enzymes generally function in anabolic pathways synthesizing end products When the end product is present in sufficient quantities the cell can allocate its resources to other uses Inducible enzymes usually function in catabolic pathways digesting nutrients to simpler molecules By producing the appropriate enzymes only when the nutrient is available the cell avoids making proteins that are not needed at that time Both repressible and inducible operons demonstrate negative control because active repressors can only have negative effects on transcription Positive gene control occurs when an activator molecule interacts directly with the genome to switch transcription on Even if the lac operon is turned on by the presence of allolactose the degree of transcription depends on the concentrations of other substrates lf glucose levels are low along with promoter overall energy levels then cyclic AMP 7 g acz c ds to cap binding site 7 I gcmeraseoperam cAMP receptor cAMp 9 825 protein CRP Q1126 122330 which activates CRP transcription azirisquotiiiiquothizWquot CRP CAP catabolite activator protein CAP used in text E coli cellular metabolism is biased toward the utilization of glucose If glucose levels are sufficient and cAMP levels are low lots of ATP then the CRP protein has an inactive shape and cannot bind upstream of the lac promoter The lac operon will be transcribed but at a low level Pr m t r DNAW lacZ 39 39 39 O erator CRP bmdlng Slte L RNA p polymerase Inactive CRP Inactive lac repressor b Lactose present glucose present cAMP level low little lac mRNA synthesized For the lac operon the presence I absence of lactose allolactose determines if the operon is on or off Overall energy levels in the cell determine the level of transcription a volume control through CRP CRP works on several operons that encode enzymes used in catabolic pathways If glucose is present and CRP is inactive then the synthesis of enzymes that catabolize other compounds is slowed If glucose levels are low and CRP is active then the genes which produce enzymes that catabolize whichever other fuel is present will be transcribed at high levels Genome Base Pairs Genes Human 3000000000 3 billion 25 30000 E coli 5000000 5 million Genome Sizes If the strands of DNA from one of our somatic cells were stretched out in a line the 46 chromosomes making up the human genome would extend more than six feet If the DNA from a single human consisting of about 100 trillion cells could be stretched out it would be over 113 billion miles That is enough material to reach to the sun and back 610 times sourceCemreronmegmed Genomics Eukaryotic chromosomes contain an enormous amount of DNA relative to their condensed length This DNA must be packaged and stored in an organized and functional manner This storage requires an elaborate multilevel system of DNA packing DNA organization begins with its association with specific proteins Chromatin refers to eukaryotic DNA and its associated proteins Roughly chromatin is composed of 13 DNA and 23 protein There are two categories of proteins associated with DNA Histone proteins and nonhistone proteins In the first level of organization the long linear DNA strand is periodically wrapped around a collection of small proteins known as histone proteins to form a nucleosome Core of eight Each nucleosome consists oft P v Vilfnemdewles molecules of each ofm different I V 39 histone proteins H2A Eight proteins HZB form the H3 histone sphere One copy of H1 clamps the DNA to the histone protein Nucleosome one histone unit including the DNA Histone proteins are positively charged with numerous lysine and arginine residues This enables histones to be attracted to DNA which is negatively charged charge comes from phosphate groups Thus there is an electrical attraction between DNA and histone proteins Each histone protein type is highly conserved This means that the amino acid sequence of each histone protein is similar among eukaryotic species For example in H4 there are 2 differences in the amino acid sequence between peas and cows in H4 146 base pairs of DNA wrap 165 times around each histone core The cores are separated by g about 200 base pairs of DNA l A mild digestion of DNA with micrococcal DNA nuclease yields a Nucleosome ladder shown at right where the nuclease has cleaved at some of the available non bound DNA between the histone cores 30 nm chromatin fiber Beads on a string DNA with nucleosomes With the aid of histone VAVAVM H1 the DNA folds into a 30nm chromatin fiber The chromatin fiber is then woven into looped domains which are attached to a nonhistone protein foundation m am my Further coiling and folding provide the metaphase chromatin m mmquot thwmescmu See page 320 for similar Figure Control of Eukaryotic Gene Expression We have approximately 25000 genes 23 pairs of chromosomes that are bundled in a compact form initiating with nucleosomes numerous tissue types multiple stages of development from zygote to aging adult Only 3 5 of a cell s genes are being expressed at any one time and gene expression is different in different tissues and at different points in development For example we do not want our brain cells making hemoglobin How is gene expression controlled uucLEus v 1 This figure outlines the possible control points for gene expression l le wa While the primary point of control of gene expression occurs at imvx l transcription each transition represents a possible control point w A Heteroch romatin represents areas of the chromosome that are not being expressed IE Um nuwuuilu WWW However heterochromatin can be ljquotquot22ln ltf converted to euchromatin through 3 chemical processes referred to as l 1 mammalquot Chromatin remodeling t The positively charged amino acids Lys K and Arg R within the Nterminal tails of histone proteins protrude from the nucleosome Chemical modification of these tails influence the expression of the associated DNA Histone Acetylation the addition of acetyl groups COCH3 to lysines of the histone tails neutralizes the positive charges on the histone tails I These amino acids can also Unacelylaxed histanes Acetylate hssrane h Acexyiazlon ol histane tails promotes loose chromalln be methylated mm ma mus quotanscripm Reducing the charge attraction between nucleosomes and DNA provides RNA polymerase and transcription factors easier access to the promoter region and permits ATPdependent chromatin remodeling factors access to open promoters Therefore histone acetylation enhances transcription while histone deacetylation represses transcription Sites of covalent 39 39 39 in histone Ntermini H4 SGRGKGGKGLGKGGAKRHRKVLRDN 3 5 E 12 I5 ED 3 Mr T A A WT H3 ARTKQTARKSTGGKAPFKQLATKAARKSA lo 910 M 1718 23 252725 M M l l H2A SGRGEQGGgARAKAKTRSSRAGLQF m M M M l I l H23 PEPAKSAPAPKKGSKKAVTKAQKKD 12 15 20 24 These modifications affect 1 chromosome structure by controlling nucleosomelnucleosome interactions 2 interactions with proteins that regulate gene expression Histone Code Hypothesis states that specific histone modification patterns provide a code that is read by transcriptional proteins 1 This code is established during embryonic development 2 Determines which genes are available for transcription in a cell 3 Thus the histone modification pattern is perpetuated in daughter cells and is responsible for gene expression patterns in specific cell types DNA Methylation is a method of inhibiting the expression of a gene Methyl groups CH3 are added to cytosines of CG pairs in DNA Genes that are heavily methylated are not expressed Genes that are heavily methylated recruit histone deacetylation enzymes together DNA methylation and histone deactylation ensure the repression of transcription DNA methylation characterizes the genes that are turned off in specific tissues Methylation patterns are passed to daughter cells of specific tissues Epigenetic Inheritance is the transmission of information from a cell or a multicellular organism to its descendants without that information being encoded in the nucleotide sequence of a gene This definition includes the modification of chromatin structure through methylation and acetylation This information is reversible without a change in DNA sequence Thus one embryo can generate a multitude of cell fates during development eg kidney cells express kidney proteins while brain cells express proteins appropriate for brain tissue Regulation of Eukaryotic Transcription Initiation In eukaryotes the transcription initiation complex binds the promoter upstreamI which is upstream of the gene The association of the RNA polymerase with the promoter is facilitated through an affiliation with a collection of proteins called transcription factors There are 100s of different transcription factors Transcription factors mediate the binding of the polymerasse to the DNA by recognizing specific aspects of the promoter the polymerase and other controlling proteins The completed assembly is called the transcription initiation complex Usumml mme r 539 quot m sun vnw mm mum 9 Several quotHumanquot 1mm Ynnin pnun harms K ammmmmupm 4mm quotquot quotmquot quot Ynmlcllyllnn mum mum39an mumquot nmniu The interaction of these general transcription factors with the promoter and polymerase leads to only a a low rate transcription Core Promoter The upstream region of a eukaryotic gene includes the promoter and several control elements which are segments of noncoding DNA that help regulate transcription by binding additional transcription factors Enhancer distal control elements DNA i I I 1 Upstream Proximal PolyA signal Termination control elements sequence reg ion Exon lntron Exon lnlron Exon it t Promme39 Downstream Transcription PolyA signal primaw RNA Exon lntron Exon lntron Exon weaved 3r end transcript 539 of primary Pre39mHNAl transcript RNA processing Cap and tail added I RNA j introns excised and mm axons spliced together Coding segment mRNA G gt 339 V W Start Stop W A v J 539 Cap 539 UTR codon cod on 3 LITE PolyA untranslated untranslated tail region region While some control elements are located close to the promoter 50 to 100 nulceoitdes others may be hundreds to thousands of nucleotides away Distal control element Activators Promoter S Gene DNA 7 l 39 I Enhancer m These more dIstant quot Genera Va transcription control elements o39iimg DNApending u protein 1 Group of are called enhancers and the transcription mediator proteins factors binding them 333mm are either activators l or repressors t 2 gt RNA synthesis Transcription initiation complex An activator is a protein that binds to a specific enhancer and stimulates enhances transcription from a Distal control I I 39 lr specific gene exemem mum prom Gm DNA I A LVJ Enhancer nu hax General transcription The DNA bends so that the en hanceractivator pair can interact with the transcription complex This interaction is facilitated by mediator proteins Transcription initiation complex DNAbending GO protein 0 Group a lactors mediator proteins RNA polymerase II RNA polymerase II J 39 RNA synthesis In addition to activators there are control elements that bind repressors that act to inhibit the expression of a gene Repressors may function by 1 blocking the binding of an activator 2 binding their own control element 3 recruiting a chromatin modifying protein such as a histone deacetylase that modifies the chromatin to a form that can not be transcribed Enhancer Prammer Enhancers typically consIst of mm mm 9mm multiple control elements each 9 of which is specific for one or mum two different transcription lt quotx g m facto rs nucleus nucleus 4 A specific combination of mm mm transcription factors will be 393 quotmmquot Wf responsible for turning on expression of a specific gene MDWW Awquot 2223 Not all control factors of an 3mm enhancer region are required I 7 k ll 39 fortranscrIptIon of the gene meringue um expressed gene a Lwercell 7 Lens cell Coordination of eukaryotic gene expression Eukaryotes do not have operons When several gene products are required for a specific eukaryotic process 1 genes may be located near each other but with distinct promoters and may benefit from the same chromatin modification that exposes related genes to transcription or 2 they may have similar control elements and activators but have unrelated locations In this case the same activators would serve to turn on genes that are located on different chromosomes PostTranscriptional Regulation Mechanisms of Eukaryotic Gene Expression The initiation of transcription is the predominant method of controlling gene expression However each additional step between transcription and protein degradation offers a point where gene expression can be controlled 5W wucraus a mm mwm wiltll tn aquot WW1 gunman A INHNA in nudqu I mmsu 4 N mm mum E t x m mam mm 1 Wmmm WWW w T Additional points in the control of gene expression RNA processing in the nucleus and the export of mRNA to the cytoplasm provide opportunities for gene regulation that are not available in bacteria ln alternative RNA splicing different mRNA molecules are produced from the same primary transcript Ems depending on which RNA DNA segments are treated as exons 1 and RNA I transcrlpt as introns RNA splicing or mRNA I ll I I l I The life span of a mRNA molecule is an important factor determining the pattern of protein synthesis Prokaryotic mRNA molecules are frequently degraded after only a few minutes Eukaryotic mRNAs may remain functional for minutes to days or even weeks The stability is depended on structural properties the mRNA For example in red blood cells the mRNAs for the hemoglobin polypeptides are unusually stable Degradation of the Poly A tail signals the removal of the 5 cap RNases enzymes that degrade RNA complete the degradation process Translation of specific mRNAs can be blocked by regulatory proteins that bind to specific sequences or structures within the 5 leader region of mRNA This prevents attachment to ribosomes Protein factors required to initiate translation in eukaryotes offer targets for simultaneously controlling translation of all the mRNAs in a cell This allows the cell to shut down translation if environmental conditions are poor for example shortage of a key constituent or until the appropriate conditions exist for example until after fertilization or during daylight in plants In the eggs of some organisms mRNAs lack an adequate poly A tail and are stored A signal in embryonic development triggers the completion of the poly A tails which enables translation Eukaryotic polypeptides must often be processed to yield functional proteins This may include cleavage chemical modifications and transport to the appropriate destination Regulation may occur at any of these steps For example cystic fibrosis results from a mutation in the gene for a chloride ion channel protein that prevents the protein from reaching the plasma membrane The defective protein is rapidly degraded Proteins do not survive indefinitely within a cell The selective degradation of a protein is another means of controlling its activity Proteins are tagged with a small protein called ubiquitin that marks that specific protein for degradation The ubiquitin tag is recognized by a protein complex called a Proteasome which digests the protein into peptides and eventually its amino acids
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