1 DNA RNA Protein.pdf

Lecture 2: DNA, RNA and Proteins Dr Timothy Fulton [email protected] Learning Outcomes LO1 – Be able to describe the structure and function of DNA, RNA and Proteins 2 The Central Dogma...

Lecture 2: DNA, RNA and Proteins Dr Timothy Fulton [email protected] Learning Outcomes LO1 – Be able to describe the structure and function of DNA, RNA and Proteins 2 The Central Dogma ull diuBion y : 中 法則 DNA sequences replicate Nucleotide sequence in DNA is transcribed into m RNA M RNA is translated to generate an amino acid sequence In some cases, RNA can be reverse transcribed to DNA Syuthesis of DNA fon RNA tenplate 3 心 Nucleotide Structure Each monomer of a DNA strand is a nucleotide Each nucleotide has a phosphate group, sugar, and nitrogenous base DNA uses deoxyribose sugar RNA uses ribose sugar These differ by the 2’ OH found in Ribose \→ DwA jfotk → RNA 4 Carbon Numbering 5 Polymer Molecules Monomer nucleotides join together to form tlgcdongerbondi twisted polymer chains ∅ stranded rreleaseb ? double - Joining nucleotides liberates water via a niparallel condensation reaction Nucleotides hydrogen bond together to form an antiparallel ladder structure 6 the join rifrogenousbase together 6 Varieties of Nucleotides singlering The structures of nucleotides determine their hydrogen bonding potential Pyrimidines hydrogen bond with purines Uracil is only found in RNA doublering 7 Complimentary Bonding The structures of nucleotides determine their hydrogen bonding potential Pyrimidines hydrogen bond with purines Uracil is only found in RNA 8  ifro minor & major bases Forming a Helix. R vibosesugarcaitfit ? bauuse pilio β - o A jrumerge The negative charges on the phosphate backbone repel each other The bases stack inside the helix structure with equal spacing between them farapart To fit the bases and ribose sugars, the backbone spirals generating a major and minor groove r The two strands must be antiparallel 9 。 The Central Dogma DNA sequences replicate Nucleotide sequence in DNA is transcribed into RNA RNA is translated to generate an amino acid sequence In some cases, RNA can be reverse transcribed to RNA 博 whencale鼠皆 re edte DNA 10  What is the Difference Between DNA and RNA? RNA uses Ribose Sugar The 2’ OH increases reactivity and reduces stability 更容易反並 RNA uses Uracil rather than Thymine This is important for DNA repair mechanisms 11 丶 What is the Difference Between DNA and RNA? 12 The Central Dogma DNA sequences replicate Nucleotide sequence in DNA is transcribed into RNA RNA is translated to generate an amino acid sequence In some cases, RNA can be reverse transcribed to RNA 13 Protein Structure Primary Structure – the order of the amino acids Secondary Structure – the structures formed as a consequence of amino acid order Tertiary Structure – higher structures formed from secondary structures Quaternary Structures – structure created from multiple polymers 14 Learning Outcomes LO1 – Be able to describe the structure and function of DNA, RNA and Proteins 15 Lecture 3: Types of RNA Dr Timothy Fulton [email protected] Learning Outcomes LO2 – Be able to describe different types of RNA and their different functions, including micro-RNAs and siRNAs 2 What are the Types of RNA? There are a huge number of RNAs - Messenger RNAs - Transfer RNAs - Ribosomal RNAs - Regulatory RNAs (micro and small interfering RNAs) 3 Messenger RNAs mRNA carries the complimentary gene sequence information from the DNA to the Ribosome mRNA is processed before translation in eukaryotes In prokaryotes, transcription and translation are synchronous nucleusi ribosome rever Eukaryo在s : trarsiption 有 anslaiun Ouurs theseume at 同步 tm { cqpio & trnslaion ocuurs at ytoplasm Pokayoes : bimultarwusly ! 4  Ribosomal RNAs → 催化功能昌 buause iti not proteins 的 洲 3) im唇 twenzye. butnonyul 9 in Non-coding RNA which is catalytic in function 去聚合 Causes amino acids from charged tRNAs to polymerase based on mRNA sequence inribosome 了 The vase majority of cellular RNA is ribosomal 催化他們合併年 trauslation 5 日 日  ② ① Transfer RNAs 片 - iniiaing ^“ ca ? 0 Poteinsynthesi ) & trnslauon ? \ where acidrs 葉草 amiho γ 6 doognateacid mno tRNAs have a stereotypical clover leaf structure ? How ④ Anticodon loop is complimentary to the codon on mRWA ③ The acceptor stem is charged with the complimentary amino acid A highly conserved sequence between organisms 6 of tRNAarroshrearly all The same alqunu organisms b Reason ? ④ 6  Regulatory RNAs wntiol Regulatory RNAs modulate expression (or translation) of other genes Interfere with translation Degradation of RNAs prior to translation Viral Regulation pathway ; 控制病毒的 式 microRNAs (miRNA) are genome encoded and regulate gene expression Q 0 Typically 23 nucleotides in length lnjechirs O ? ≥ Small interfearing RNAs (siRNA) use a similar mechanisms but are exogenous (viral) 外來的 ( 病毒性的了 7 。 方 miRNA siRNA Regulation of Gene Expression θ wuld bemiRNA / siRNA ? r √ 8 Learning Outcomes LO2 – Be able to describe different types of RNA and their different functions (storage, messenger, catalyst, scaffold – mRNA, tRNA, rRNA, snRNA, scRNA) 9 BMD164: Genetics Dr Timothy Fulton [email protected] Module Schedule Week 1 – 4 – Dr Fulton - Genomes and Genome Organisation Week 5 – 6 – Dr Bulgakova– Mendelian Genetics Video Presentation Task Week 7 – Preparing for your Practicals, but this is not half term MCQ Test (Week 1-6) Week 8-9 – Dr Fulton – Transcription and Translation Week 10-11 – Prof Munroe – Regulating Gene Expression Week 12 – Dr Fulton – Molecular Technologies January – Final Exam 15 Practical Classes (BMD164) A three week mini-project Modern molecular genetics techniques Check your timetables! 16 Assessments 60% Coursework & 40% Exam - Coursework – Video Presentation Week 5 and 6 – 50% - Programme Coursework – Week 10 – 10% - Exam – MCQs and Programme Level Short Answer Questions – 40% Mock MCQ Exam: Week 7 – Does not count, but you should do it!! Everything from QMplus, live lectures and practicals can be examined All assessments test understanding, not factual recall “I’m sick during an assessment, what should I do?” 17 DNA, RNA and Proteins Dr Timothy Fulton [email protected] Learning Outcomes LO1 – Be able to describe the structure and function of DNA, RNA and Proteins LO2 – Be able to describe different types of RNA and their different functions (storage, messenger, catalyst, scaffold – mRNA, tRNA, rRNA, snRNA, scRNA) 20  The Structure of DNA 5 thend 6 phosphate Aderine End? 3 2 purine Gases 也在外 的是 Guarine 7 4 第5 星 mad 1 deoxyribose Cytosine 5 pyramicline bases 8 hymine 6 End? 3 rdend 21 。 斤 面 Identifying Nucleotides ATCGU A G 1 2 T c 3 4 5 22  What are the differences between RNA and DNA? bealacked by chenicals thaH DWAis morestable thanRrt Oigroup i3 morl hikely to. , ho 1 ^ dt 2 IrdoH I RNA donblestrmded singlestraucded deoxyribose ribose ( znd Hfstable lindoyfunstabel Celigibltobe Thymine Uracrl a艹 ackel by chamiials ) hhorter 做 kagui nmleoides 都 nucleus ( NAwnvetgeetivinbe formedinnucleolus 兄 kii) 1 , RuA is more but move Outofnuclem esiitmeto Vulherableto UVlight tor dilterutreasons ov light 23 。 Why is DNA a Better Storage Molecule Compared to DNA? 服 DNA is more stable stable ReasonI ; DNAis doublerstrmdld , 3 Dshape _ fuctually Reusonz t has deoxyribose Sugar : 1 is eligible tobe aHaced ) chenically stable - : 2 H ( not 24  Why might DNA, RNA and Protein All be Considered Directional Molecules? 3 5 - lthas ' & end Proteinhas difwentend. direchonal - 慶 :it ensurls tMat transcripion & trmslaton ocuurs in anorgarised andumiform manner. w oDNAsequene dorieger messedup 25 用 Messenger RNAs mRNA carries the complimentary gene sequence information from the DNA to the Ribosome mRNA is processed before translation in eukaryotes In prokaryotes, transcription and translation are synchronous Why can prokaryotic mRNA be translated at the same time as it is transcribed? U Blcuuse it doesit have Mucleus , 80 DNA R RNA ane ntthesomearea IuRWA i3 poluudinthe ytoplasm inpokayotes) 28  Ribosomal RNAs charged ? rphg iTit Non-coding RNA which is catalytic in function hotenzyme. it;notpotein ) Transfers amino acids from charged tRNAs to peptide polymer based on mRNA sequence in ribosomes cprotein ) The vast majority of cellular RNA is ribosomal ktranslaha Considered good evidence for the RNA World Theory - Ribosomes are needed to make Proteins - Which came first? Chicken and Egg arguments. 29 。  RNA World Hypothesis : life on Earth begnwith a Simple RNA molemu thatwuld ω pYitseifwithouthelp omother moleules Life began (or pre-biotic) as a self-replicating RNA molecule - RNA has catalytic function - RNA has storage function ( xNAhasbame function - RNA can √ sometimes self replicate 1f 8 pyitse-4 2 ω. d lmustcaitdoiel , ex. bingle struded. Viroids – Naked circular ssRNA which infect plants ( Doit infetanimals) ∅ - Replicate in a host cell imallrumberofit - A relic of the RNA world? 遺跡 b Like Virns - A newly derived retrotransposon? 30 。 心 Transfer RNAs aninoacidbinding sife tRNAs have a stereotypical clover leaf structure Anticodon loop is complimentary to the codon The acceptor stem is charged with the complimentary amino acid A highly conserved sequence between organisms 的 Doitchange thesequend ney allogamisms. in lwhy ? ” cumplenentayd 31  Alvantuge : ellscn ωnol whiihgne gettruscribed ac( which truscript get trmidaed Regulation of Gene Expression by RNAs → Good tool tomedicine ? 18 How to onTrol Ge why ? xpres in 1. ( 控制胡問題的基因 ) ① strmcud ② ? BNAdunhle 熊品 Double Stranded RNAs detected by _ ? Nubcune Argonaute Proteins hhy ) i hin e ⑤ why zl ? Cut into 21 nucleotide ssRNA pieces micro RNA Target Argonaute protein to other RNAs by base pair rules A hoildingokeyandtyalthe Rerson Argonaute protein regulates expression Yhingle atrand lock mtil find ore RrA ④ → rompma ③ Can you think why this might be a good Difference d pathway to manipulate for research, or 斷 新制 tuNy belween 上形成 染 質使講被tmud 在比 A medical treatments? Brevertdiseases cancers ) these thre ? 掉 target hh 0 ( 再破摔 / - Towntrolabnormalgneexpression RrA 32 一 。 黑 色 Regulation of Gene Expression by RNAs Double Stranded RNAs detected by Argonaute Proteins Cut into 21 nucleotide ssRNA pieces Target Argonaute protein to other RNAs by base pair rules Argonaute protein regulates expression How would you get a siRNA drug into a cell? What do you need to think about? 33  Regulation of Gene Expression by RNAs Exmpl. ① iBNy Diagram Hereditary Transthyretin Amyloidosis Drug: Onpattro Inhibits synthesis of Transthyretin Protein in ∵ Liver Pwduetoomuch Liver L0 - Gedigested by ostomachacid How would you administer this drug? Pill? Injection? Inhalation? Why? Why administer using a Lipid Nanoparticle?→ Tob比 bolubletothe In any drugs trial, what should you consider? How do we Krow where it willbeexpresiedmenbrane ( ? 10 also lipidibilayer ) 34 。  lowwould you admimister thisdrug ? What should You onside in clug tvial ? ③ - |: X , as itwrl bedigeredbystomach acid. - Cheright. well bung of the 在 ial subjects. inhalaion : X Beuuseainay doesit gototiverl - feasibilily ② : , diretly to blood lnjecion risks - - V - cω st Why Vipidnanoparrides benefits imeirlast liplid ~ Membrnl is phos 的 holipidbilaye , Couldbemone Soluble , md suallpartidealso innlase solabikly 。 一  Learning Outcomes LO1 – Be able to describe the structure and function of DNA, RNA and Proteins LO2 – Be able to describe different types of RNA and their different functions (storage, messenger, catalyst, scaffold – mRNA, tRNA, rRNA, snRNA, scRNA) ∞ sMall wncdihonal RWA Qsmall nuclear RNA omeasuretheexpressionleuel bprovide Structwral hupport for d of eachgeneacross of ells Ullatlachment ud Subieuut apopulauon orpre _ mRUA intron splicing isbue denecopmert 35 。