Presentation on theme: "Introns and Exons DNA is interrupted by short sequences that are not in the final mRNA Called introns Exons = RNA kept in the final sequence."— Presentation transcript:
1 Introns and ExonsDNA is interrupted by short sequences that are not in the final mRNACalled intronsExons = RNA kept in the final sequence
2 Gene RegulationAbility of an organisms to control which genes are present in response to the environment
3 Prokaryotic cells turn genes on and off by controlling transcription. A promotor is a DNA segment that allows a gene to be transcribed.An operator is a part of DNA that turns a gene “on” or ”off.”An operon includes a promoter, an operator, and one or more structural genes that code for all the proteins needed to do a job.Operons are most common in prokaryotes.The lac operon was one of the first examples of gene regulation to be discovered.The lac operon has three genes that code for enzymes that break down lactose.
4 The lac operon acts like a switch. The lac operon is “off” when lactose is not present.The lac operon is “on” when lactose is present.
6 Points of controlThe control of gene expression can occur at any step in the pathway from gene to functional protein1. packing/unpacking DNA2. transcription3. mRNA processing4. mRNA transport5. translation6. protein processing7. protein degradation
7 1. DNA packing as gene control Degree of packing of DNA regulates transcriptiontightly wrapped around histonesno transcriptiongenes turned offheterochromatindarker DNA (H) = tightly packedeuchromatinlighter DNA (E) = loosely packedHE
8 DNA methylation Methylation of DNA blocks transcription factors no transcription genes turned offattachment of methyl groups (–CH3) to cytosineC = cytosinenearly permanent inactivation of genesex. inactivated mammalian X chromosome = Barr bodyMethylation results in a human disease called fragile X syndrome; FMR-1 gene is silenced by methylation.
9 Histone acetylation Acetylation of histones unwinds DNA loosely wrapped around histonesenables transcriptiongenes turned onattachment of acetyl groups (–COCH3) to histonesconformational change in histone proteinstranscription factors have easier access to genes
10 FigMethylation of H19 inactivates transcription(involved in expression of insulin like growth factor)
11 Fig aChromatin remodelingAcetylation of histones enhances access to promoter region and facilitates transcription.
12 Epigenetic Inheritance Although the chromatin modifications just discussed do not alter DNA sequence, they may be passed to future generations of cellsThe inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance
13 2. Transcription initiation Control regions on DNApromoternearby control sequence on DNA (TATA box )binding of RNA polymerase & transcription factors“base” rate of transcriptionenhancerdistant control sequences on DNAbinding of activator proteins“enhanced” rate (high level) of transcription
14 Model for Enhancer action Enhancer DNA sequencesdistant control sequencesActivator proteinsbind to enhancer sequence & stimulates transcriptionSilencer proteinsbind to enhancer sequence & block gene transcriptionMuch of molecular biology research is trying to understand this: the regulation of transcription.Silencer proteins are, in essence, blocking the positive effect of activator proteins, preventing high level of transcription.Turning on Gene movie
15 Transcription complex Activator Proteins• regulatory proteins bind to DNA at distant enhancer sites• increase the rate of transcriptionEnhancer Sitesregulatory sites on DNA distant from geneEnhancerActivatorActivatorActivatorCoactivatorBFERNA polymerase IIATFIIDHCoding regionT A T ACore promoterand initiation complexInitiation Complex at Promoter Site binding site of RNA polymerase
16 Promoter Activators Gene DNA Enhancer FigPromoterActivatorsGeneDNADistal controlelementEnhancerTATAboxGeneraltranscriptionfactorsDNA-bendingproteinGroup ofmediator proteinsRNApolymerase IIFigure 18.9 A model for the action of enhancers and transcription activatorsRNApolymerase IITranscriptioninitiation complexRNA synthesis
17 3. Post-transcriptional control Alternative RNA splicingvariable processing of exons creates a family of proteins
18 RNA processing is also an important part of gene regulation in eukaryotes. mRNA processing includes three major steps.Introns are removed and exons are spliced together.A cap is added.A tail is added.
19 Regulation by alternative splicing Calcitonin gene-related peptide
20 4. Regulation of mRNA degradation Life span of mRNA determines amount of protein synthesismRNA can last from hours to weeksRNA processing movie
21 5. Control of translation Block initiation of translation stageregulatory proteins attach to 5' end of mRNAprevent attachment of ribosomal subunits & initiator tRNAblock translation of mRNA to proteinControl of translation movie
22 6-7. Protein processing & degradation folding, cleaving, adding sugar groups, targeting for transportProtein degradationubiquitin taggingproteasome degradationThe cell limits the lifetimes of normal proteins by selective degradation. Many proteins, such as the cyclins involved in regulating the cell cycle, must be relatively short-lived.Protein processing movie
23 Concept 18.3: Noncoding RNAs play multiple roles in controlling gene expression Only a small fraction of DNA codes for proteins, rRNA, and tRNAA significant amount of the genome may be transcribed into noncoding RNAsNoncoding RNAs regulate gene expression at two points: mRNA translation and chromatin configuration
24 RNA interference NEW! Small interfering RNAs (siRNA) short segments of RNA (21-28 bases)bind to mRNAcreate sections of double-stranded mRNA“death” tag for mRNAtriggers degradation of mRNAcause gene “silencing”post-transcriptional controlturns off gene = no protein producedsiRNA
25 Action of siRNA siRNA mRNA degraded functionally turns gene off Hot…Hot new topic in biologyAction of siRNAdicer enzymemRNA for translationsiRNAdouble-stranded miRNA + siRNAbreakdown enzyme(RISC)mRNA degradedfunctionally turns gene off
26 Gene Regulation 7 6 protein processing & degradation 1 & 2. transcription- DNA packing- transcription factors3 & 4. post-transcription- mRNA processing- splicing- 5’ cap & poly-A tail- breakdown by siRNA5. translation- block start of translation6 & 7. post-translation- protein processing- protein degradation54initiation of translationmRNA processing21initiation of transcriptionmRNA protectionmRNA splicing43
27 Cancers result from a series of genetic changes in a cell lineage The incidence of cancer increases with age because multiple somatic mutations are required to produce a cancerous cellAs in many cancers, the development of colon cancer is gradual
28 Eukaryotic Gene Regulation Hox genes – controls differentiation of genesResponsible for general body pattern of most animalsOrder of genes is order of body parts
30 Review questionsWhat does DNA polymerase do? What does Helicase do? What does ligase do? Match the bases below. 5’ – A T C G T A – 3’ List 3 differences between RNA/DNA. What are the 3 types of RNA? Where does RNA go after it is made? Transcribe the DNA below. A T C G T A
31 What does RNA attach to when it leaves the nucleus What does RNA attach to when it leaves the nucleus? Amino Acids are the building block of ________. What type of RNA brings an amino acid? When does translation stop? Where is the codon located? Anticodon? What is a codon? Translate the mRNA strand below. A G C G A G Translate the DNA strand below ATG CTA TGCA