H1 85 mst 1 comprehensive notes for mcb PDF

Preview

Summary

course summary for mst1...

Description

BIOM20001(MCB(

1

TM1 TM1$$ MOLECULES(OF(THE(CELL(

What%is%life?% • “Living(things,(though(infinitely(varied(when(viewed(from(the(outside,(are(fundamentally(similar(on( the(inside”((Alberts(5ed(p(1.)( • Astonishing(variety(in(individual(particulars:(appearance/form( o Tiger,(seaweed,(bacterium,(tree( • Astonishing(constancy%in%fundamental%mechanisms( o DNA,(transcription,(translation,(protein(synthesis,(metabolism( • Astonishing(constancy%at%a%molecular%level( o Structure(of(biological(molecules( o Physicochemical(properties( o How(they(interact( o Energetic(basis(for(self-assembly,(folding,(enzyme(catalyzed(reactions( • Don’t(need(magic,(Ka,(vital(spark,(Odic(force( o Hydrogen,(carbon,(nitrogen,(oxygen,(sulfur,(phosphorus(etc.( o Covalent(and(noncovalent(interactions( • Life(exists(because(the(molecular(processes(of(self-assembly(and(inheritance(are(spontaneous( under(the(appropriate(conditions:(hydration,(concentration,(temperature,(pressure(etc.( ( Life%of%earth%is%protein-based% • ‘Final’(products(of(gene(expression( • Major(dry(weight(component(of(cells( • Major(structural(‘building(block’(in(cells( • Most(cell(functions(performed(by(proteins(( • Protein(structures(are(fascinating(and(beautiful( • Proteins(act/execute:( o As#building#blocks#e.g.(cytoskeletal(actin(filaments,(viral(capsids(# o Chemical#reactions#e.g.(enzymes:(lysozyme,(chymotrypsin# o As#Channels#and#pumps#e.g.(Ca2+(pump(or(Ca2+(ATPase(Proteins(# o Transmit#cell#signals#e.g.(EGFR,(Src,(Ras(GTPase# o As#molecular#machines#e.g.(motor(proteins:(myosin,(kinesin(# o Other#specialised#proteins#act#as:#Antibodies,(toxins,(hormones,(antifreeze,(elastic(fibres,( ropes,(luminescence# • DNA(Mutation(à(protein(evolution((i.e(fluorescent(protein(in(different(colours((cyan,(yellow,(blue))( o Sequence(à(Structure(à(Chemistry(à(Activity( ( THERMODYNAMICS% • Gibbs(free(energy(depicts(how(the(reaction(of(reactants(( and(products(are(going(to(happen( • It(is(the(energy(of(the(reaction(available(to(do(work( • Also(called(the(“available”(energy((note(temperature(dependent((K))( ( Enthalpy%=%Heat%Energy% Entropy%=%Disorder% Gibbs%free%energy%takes%account%of%enthalpy%and%entropy%

∆G%=%∆H%−%T∆S%=%Gproducts%–%Greactants%%

2 (

(

BIOM20001(MCB(

SPONTANEOUS%REACTIONS% • If%∆G%is%negative,%then%the%reaction%is%spontaneous% • Given(by:% o Big%negative%∆H%(Exothermics)% o Big%positive%∆S%(increase%in%entropy)% % Exergonic:%∆G%is%negative:%Free%energy%released:%Favourable:%Spontaneous% Endergonic:%∆G%is%positive:%Free%energy%absorbed:%Unfavourable:%Not%Spontaneous% % Exothermic:%∆H%is%negative:%Heat%released% Endothermic:%∆H%is%positive:%Heat%absorbed% % FREE%ENERGY%AND%EQUILIBRIUM% aA%+%bB%↔%cC%+%dD%

%

%

"#$ =

' & '#$( ) #$ ' * '#$( + #$

%

Keq(is(the(thermodynamic(equilibrium(constant(for(the(reaction(( It(describes(the(“position”(of(the(reaction(at#equilibrium( o i.e.(the(relative(concentrations(of(components(at(equilibrium(( • [X]eq(is(the(concentration(of(component(X(at(equilibrium( • Little(k(is(the(rate(constant( & '5 ( ) 56 ,- = ,./ + (12(34 7 % * 5 ( + 85 • ∆G(is(the(actual(free(energy(change(for(the(reaction;( • It(describes(how(much(work(the(reaction(can(do;(and(it(depends(on:(( o (i)(∆Go(the(standard(free(energy(change(( § A(constant(for(the(particular(reaction;(measured(under(standard(conditions( o (ii)(The(initial(concentrations(of(the(reactants(and(products( § [X]i(is(the(initial(concentration(of(component(X( • Further(away(from(equilibrium(you(start;(the(more(work(is(done(before(you(get(there(( • R(is(the(universal(gas(constant;(T(is(the(temperature(in(K( • At(equilibrium,(∆G(=(0;(The(reaction(can(do(no(more(work( • Rearranging(the(equation(gives:( ,./ = ( −12(34"#$ ( STANDARD%CONDITIONS% % • •

,./ % •

%

Use(of(standard(conditions(allow(free(energy( changes(to(be(easily(compared(Chemistry(and( Physics(standard(conditions(–very(general( o 298(K((25(°C)( o Gases(at(a(partial(pressure(of(101.3(kPa( (1(atm)( o Reactants(and(products(at(1(M( concentrations( o i.e.[H+]=1M→pH(0%

,.:/% • •

•

Biochemistry(standard(conditions(–rather( specific( As(above(except:(reaction(occurs(in(a(well( buffered(aqueous(solution(at(pH(7( o [H+](and(Mg2+( § »([H+](=(10-7(% § »(Mg2+(=(1(mM((needed(for( enzymes)% For%all%biochemical%reactions,%assume% biochemical%standard%state%

BIOM20001(MCB(

3

% USE%OF%FREE%ENERGY% • Predictive(power( • If(you(know(the(standard(free(energy(change,(you(can(answer(these(questions:( o Under&what&initial&conditions&will&a&reaction&occur&spontaneously?& o Does&the&reaction&need&to&be&coupled&with&a&favourable&reaction?& o What&is&the&position&of&the&reaction&at&equilibrium?& o Theoretically,&how&much&work&can&this&reaction&do?& & MAKING%“UNFAVOURABLE”%REACTIONS%GO% • The(measure(of(whether(a(reaction(will(proceed(spontaneously(is(∆G(not(∆G’o% & '5 ( ) 56 / ,- = ,. + (12(34 7 % * 5 ( + 85 • So,(if(even(∆G’o(is(positive(∆G(can(be(negative(by(altering(the(initial(conditions% & '5 ( ) 6 5

%to(be(a(negative(number,(

& '5 ( ) 56

%5MJ)' o This(can(represent(1%(of(muscle(weight(after(a(mean((other(25%(stored(in(liver)' • RESTING'CONDITIONS' o Utilizes(fatty(acids(as(major(fuel((85%(of(energy)' o Heart(muscle(uses(one(of(the(ketone(bodies((acetoacetate)(in(preference(to( glucose((also(metabolites(are(connected(with(liver(by(the(Cori(Cycle)' ' Adipose4 • FUEL'SOURCES' o Glucose(required(to(perform(major(task(of(synthesizing(and(storing( triacylglycerol,(which(is(mobilized(during(fasting' • FUEL'STORES' o In(70kg(person,(adipose(stores(>80%(of(total(available(energy((565(MJ( or(15kg)' • RESTING'CONDITIONS' o Highly(active(during(starvation((↓(insulin(activates(hormone-sensitive( lipase(which(breaks(down(TAG)( ' ' Liver4 • FUEL'SOURCES' o Glucose,(fatty(acids,(ketone(bodies(and(amino(acids' o Prefers(⍺-keto(acids(derived(from(the(degradation(of(amino(acids(in(preference(to(glucose' • FUEL'STORES' o Stores(¼(of(total(body(glycogen' o Uses(lactate(&(alanine(from(muscle,(glycerol(from(adipose(&(glucogenic(amino(acids(from( diet(to(make(~200(g(of(glucose(per(day(via(gluconeogenesis' • RESTING'CONDITIONS' o Highly(active(during(starvation(making(glucose(via(GNG(to(maintain(blood((glucose)( primarily(for(the(brain(and(RBCs' o Also(oxidises(fatty(acid’s(for(energy(and(formation(of(KBs(for(the(brain,(heart(muscle(&(other( tissues' • OTHER'FUNCTIONS' o Altruistic(organ:(synthesizes(TAGs,(PLs(&(cholesterol(&(secretes(as(VLDL(for(lipoprotein( transport(&(synthesizes(heme'

76 !

!

BIOM20001!MCB!

TM16 TM16%% HORMONAL!REGULATION!OF!METABOLISM!

The$Fasting$State$ • Drop!in!blood!glucose!below!4.5$mM$triggers!glucagon! release!from!the!pancreas:!resting![glucose]!blood!=!5.0$ mM! • Glucagon!causes!an!increase!in!blood!glucose!levels! • Glucagon!activates!gluconeogenesis!(GNG)!&! glycogenolysis!(GGL)!in!the!liver! • Glucagon!inhibits!glycolysis!(GL)!and!glycogenesis!(GG)! o Glucose!is!sent!to!priority!tissues:!brain!and!red! blood!cells! § RBCs!lack!mitochondria!so!rely!on! glycolysis!for!energy!to!stay!alive,!so! need!glucose!all!the!time!(low!KM)!also!lacking!a!nucleus! $ SIGNAL$TRANSDUCTION$PATHWAYS$ GLUCAGON( Pathway$ $ $ $ $ $ $ $ $ $ $ • Glucagon$ o 1°!messenger$ o Peptide!hormone!(29!AAs,!Mr!=!3,483)! o Synthesized!in!the!α$cells!of!the!pancreas! ! o Secreted!into!the!blood!when![glucose]blood!drops!20%(Lysines(and(Arginines)(and(DNA(is( negatively(charged(due(to(the(phosphate(groups,(this(helps(DNA(and( histones(bind(tightly( • Help(package(DNA( (

86 (

(

BIOM20001(MCB(

Chromatin(Forms( • Euchromatin( o Open(and(accessible(to(other(molecules( o Used(for(transcription( • Heterochromatin( o Highly(compacted(and(condensed( o Generally(not(transcribed( o Found(in(some(regions(where(there(are(few( genes((i.e(telomeres(and(centromeres)(and( silent(genes( ( Histone(Tails( • Part(of(the(protein(is(globular(but(part(of(the(protein( hangs(out,(so(a(nucleosome(have(8(tails(hanging(out( • Just(know(that(these(tails(can(be(chemically(modified( and(changes(their(properties( • Can(provide(new(binding(sites(for(proteins(that( regulate(chromatin(state( o Acetylation((reduces.+ve.charge.of.histones.so. attraction.between.DNA.and.histones.is.less,. therefore.less.bound.strength)( o Methylation( o Phosphorylation( o Ubiquitination( • Different(modifications(have(specific(“meaning”(to(the(cell,(causing(the(histone(“code”( o H3Kme3( § This(modification(leads(to(highly(compacted(heterochromatin((more(in(Lectures( 28/29(by(MB)( § Histone.3,.20th.Amino-acid,.3.methyl.groups.added( o H4K20me2( § Histone.4,.20th.residue,.2.methyl.groups.added( ( Origins(of(Replication( • A(location(on(a(chromosome(where(DNA(replication(is(initiated( • Eukaryotes(have(multiple(origins(on(each(linear(chromosome( o AT-rich((easier(to(separate(the(two(DNA(strands(because(of(2(H-bonds)( o Enriched(for(H4K20me2((binding(site(for(ORC)( ( EUKARYOTES:(DNA(replication(initiation( 1. ORC((origin(replication(complex)(consists(of(6(proteins.( ORC1-6(that(binds(to(the(origin.( ( 2. Prereplicative(complex(completed(by(DNA(helicase(binding.( Now,(we(wait(for(S-phase(to(begin(as(well(as(activation(signal( ( 3. At(S-phase,(kinases((cyclins)(become(active.(Helicase(is( phosphorylated(and(activated,(melting(A-T(rich(area.(ORC(is( phosphorylated(and(deactivated((can’t(recruit(a(new(preRC).( DNA(polymerase(is(loaded(and(the(two(replication(forks(head( off(in(opposite(directions((revise(DNA(replication(from(1st(yr)(

BIOM20001(MCB(

87

Reaching(the(ends(of(chromosome(in(DNA(replication( • Leading(strand(is(good,(can(be(replicated(right(to(the(end( • Lagging(strand(is(a(problem,(because(the(last(part(of(the(chromosome((where(the(final(RNA-primer( was(placed)(cannot(be(replicated(with(DNA( o Exonucleases(will(remove(this(single-stranded(overhang( o After(each(cell(cycle,(chromosomes(LOSE(~50-100bp( o Normal(process(is(somatic(cells((divide(50-70(times(before( senescing,(ceasing(division)( o OPPOSED(by(TELOMERES(AND(TELOMERASE( ( Telomeres( • A(protective(structure(at(both(ends(of(a(linear(chromosomes,(consisting(of(a(tandem(repeat(of(the( sequence(GGGTTA,(and(associated(proteins,(which(serves(to(maintain(the(integrity(of( chromosomes((associated(with(aging;(Werner(Syndrome)( • Protect(the(ends(of(chromosomes(from(loss( of(base(pairs( • Chromosomes(lacking(telomeres(are( unstable(and(may(be(susceptible(to( chromosomal(rearrangements(such(as( fusion( o Retrotransposons(jumps(in(a(spot(with(genes((evolves(out)(but(if(they(gather(in(the( subtelomeric(region(it(is(not(a(problem(so(can(built(up(here( ( Telomerase( • A(ribonucleoprotein((protein(+(RNA)(that(elongates(telomere( sequences( o Blue(part:(The(RNA(portion(has(the(sequence( CUAACCCUAAC(which(is(complementary(to(the(telomere( repeat((TTAGGG)n( o Bottom.green.part:(Protein(component(called(TERT(which( has(reverse(transcriptase(activity( • KEY(POINT:(Telomerase(does(NOT(fill(in(the(gap,(but(extends(the( 3’(end(of(the(overhanging(strand( ( 1. Telomerase(binds(to(3’(end(of(the(telomere(that(is(complementary( to(the(telomerase(RNA( ( ( 2. Bases(are(added(by(the(TERT(reverse(transcriptase,(using(the(RNA( as(a(template( ( ( 3. Telomerase(relocates( ( ( ( ( 4. DNA(polymerase(then(complements(the(lagging(strand( ( (

88 (

(

BIOM20001(MCB(

Human(Centromeres( • The(heterochromatic(region(of(a(chromosome,(which(joins(sister(chromatids(during(mitosis( • Region(to(which(microtubules(attach,(via(the(kinetochore( o Pericentric(regions((blue)( § Flank(centric(region( § Often(rich(is(LINEs(and(SINEs( o Centric(regions((red)( § Consists(of(a(tandem(repeat(of(171bp( sequence(called(the(alpha-satellite(repeat( § 1500(to(30,000(of(these( ( ( ( ( ( ( § Consists(of(alternating(regions(in(which( the(Histone(H3(is(either(dimethylated(at( K4,(or(is(replaced(by(a(variant(of(H3( which(is(only(found(in(centromeres,( called(CENP-A( § CENP-A(is(important(for(assembly(of(the( kinetochore( ( ( Chromosomal(Aberrations( • Gain/loss(of(whole(chromosomes( • Duplications(or(deletions(of(parts(of(chromosomes((can(be( pseudogene(evolution)( • Chromosomal(fusions((caused(by(2(loose(ends)( • Reciprocal(translocations( ( ( Centromeres(and(chromosomal(abberrations( • Non-disjunction(–(failure(to(attach( • Random(segregation(due(to(no(centromeres( • Multiple(centromeres(causing(chromosome(breakage( • Translocations(due(to(inappropriate(crossing-over(during( meiosis( ( Special(Cases:((Trisomy(21(–(Down(Syndrome( • Physical(growth(delays( • Characteristic(facial(features( • Mild/moderate(intellectual(disability( • ~1/1000(births( • 3(copies(of(chromosome(21,(most(due(to(meiotic(non-disjunction( o Usually(trisomy(means(cell(cannot(continues(to(grow(because(too(drastic(change(( • 2-3%(due(to(Robertsonian(translocatio( ( (

BIOM20001(MCB(

89

( Robertsonian(translocations( • Acrocentric(chromosome( o Where(the(centromere(in(the(chromosome(is(located(close(to(the(end(of(the(chromosome( o Human(has(5(acrocentric(chromosomes((13,(14,(15,(21,(22)( • Robertsonian(translocation( o Two(chromosome(joining(at(the(centromere(region( o Occur(in(1/1000(births( o Most(common(between(chromosomes(13(and(14( • Mechanism( o The(short((p)(arms(of(the(acrocentric(chromosome(do(not( contain(any(essential(genes(but(contain(tRNA(and(rRNA( loci(which(are(present(in(multiple(copies( o Breakage(of(the(centromeric(region(in(normal( chromosome( o Causes(centromeric(fusion(into(one(chromosome( • Can(lead(to(trisomy( o Parent(unaffected(and(is(the(one(with(the(translocation,( but(is(balanced(so(gene(expression(is(not(affected( drastically,(if(at(all( o Offspring(may(be(affected( ( ( Mutagens( • DNA(is(constantly(being(damaged(and(repaired( • Mutagens(lead(to(DNA(damage(and(then(repair(processes( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (

90 ( •

(

BIOM20001(MCB(

Two(most(common(changes(are(Depuration(and(Deamination( o Depuration( § Hydrolytic(attack( § Results(in(loss(of(purine( § Replaced(with(OH(group( • Can(cause(1bp(deletions( o Deamination( § Hydrolytic(attack( § Results(in(loss(of(NH2( § Replaced(with(double(bond(O( § Changes(base(to(Uracil( • Can(lead(to(G(à(A(mutation( (

( ( ( ( ( ( ( ( ( ( ( ( ( (

• ( ( (

( UV(light(can(cause(pyrimidine((e.g(thymine)(dimers( o Causes(a(distortion(of(the(DNA(on(one(strand(

(

BIOM20001(MCB(

91

MM MM20 20 20$$ TRANSCRIPTION(AND(TRANSLATION(

Summary' • Protein(binds(to(promoter,(transcription(of(DNA(into(primary(RNA( • Gets(modified,(with(a(cap(on(the(5'(end,(sequence(at(the(end(clipped(out(to(reduce(excess(RNA( • Polyadenylation(occurs( • Splicing(occurs((finds(particular(sequences,(binds(to(those(and(snips(introns(out)(and(reduces( message(size( • This(RNA(is(now(mature(RNA(and(is(now(ready(for( translation( • Protein(binds(to(cap(and(finds(AUG((start(codon)(ribosome( assembles( • Chugs(along(3(bases(at(a(time(à(producing(polypeptide( and(longer(grow( • Comes(to(particular(codon((UAA)(which(is(a(stop(codon( • Release(factor(binds(to(UAA(and(whole(thing(falls(apart( and(we(are(left(with(the(polypeptide( ( Transcription' • Copying(of(one(strand(of(DNA(into(a(complementary(RNA(sequence(by(the(enzyme(RNA(polymerase' • Many(types(of(RNA(are(transcribed' o mRNA( messenger(RNAs,(code(for(proteins' o rRNA( ribosomal(RNAs,(form(basic(structure(of(ribosome,(catalyse(protein(synthesis(' o tRNA( transfer(RNAs,(needed(for(p.synthesis(as(adaptors(b/w(mRNA(+(AA' o snRNA( small(nuclear(RNAs,(nuclear(processes(including(slicing(of(pre-mRNA' ' RNA'polymerase' • Enzyme(that(catalyses(the(synthesis(of(an(RNA( molecule(on(a(DNA(template(from(ribonucleoside( triphosphate(precursors' • Types(of(RNA(polymerases' o Eukaryotes(are(based(on(the(prokaryotes( but(have(more(complex(differences( ' ' ( ( ( ( ( ( ( ( ( ( ( '

92 (

(

BIOM20001(MCB(

Prokaryotic'RNA'polymerase' • Core'enzyme' o Responsible(for(polymerisation(is(composed(of(5(subunits' • Sigma'Factor' o Only(needed(to(initiate(transcription' • Holoenzyme' o Core(enzyme(and(sigma(factor(when(bound(together' ' Prokaryotic'Transcription'Initiation' • σ'factor'kick-starts(the(whole(process(by(binding(to(the(σ(binding(sites((35,(-10(regions(for(orientation(of(the(polymerase)(in(the(promotor( sequence(and(then(the(RNA'polymerase'binds'and(can(start(the( transcription((more(detail(next(lecture)' ' Eukaryotic'Transcription'Initiation' • Promotor(is(more(variable(and(complex(than(in( prokaryotes' • Initiation(complex(involves(many(more( proteins/factors:' o General(Transcription(Factors' o RNA(polymerase(II' o Mediator(complex' o Transcriptional(Activators' o Chromatin(remodelling(complexes' o Histone-modifying(enzymes' ( General'Transcription'Factors' • Needed(to(initiate(transcription(of(all'genes' • There(are(many(factors,(but(we(are(interested(in(TFIID'and'TFIIH' • Similarly(to(prokaryotes,(eukaryotic(promotors(have(a(key(recognition(region( called(the(TATA'box(which(is(A/T(rich' ' TRANSCRIPTION'–'INITIATION'(RNA'pol'II)' • Transcription( begins( when( the( TFIID' binds' to' the' TATA' box' via( one( of( its( components,(the(TBD'(TATA'Binding'Protein)' o The( TFIID( complex( also( has( 11( other( proteins( called( TAFs( (TBPAssociated(Factor)' • Next,(other(GTFs(and(RNA(pol(II(bind,(to(form(the(“pre-initiation(complex”(' • Now,(TFIIH'activates'transcription(by:' o With(its(helicase(activity,(it(unwinds(the(DNA(at(the(TATA(box' o With(its(kinase(activity,(it(phosphorylates(the(C-Terminal(Domain(tail(at(Ser-5' o Amongst(other(factors((e.g(chromatin(remodeling(complex(which(helps(get(access(to(DNA)' ' Key'structures' • Mediator' • C*Terminal*Domain*(CTD)' o Key(regulatory(region(of(RNA(pol(II' o Consists(of(52(tandem(repeats(of(a(7-amino-acid(motif(with(Ser(at(positions(2(and(5' o Phosphorylation(of(Ser5(affects(conformation(and(activity(of(RNA(pol(II,(releasing(it(to(begin( transcription'

BIOM20001(MCB( TRANSCRIPTION'–'ELONGATION'(RNA'pol'II)' • Elongation(is(where(the(RNA(strand(produced(gets(longer' • When(Ser5(is(phosphorylated,(capping'proteins'bind'to'the'CTD' ' ' • As(the(end(of(the(newly(generated(mRNA(emerges,(the(capping( proteins(can(leave(the(tail(and(bind(to(the(mRNA' o After(about(20-30(nucleotides(have(been(transcribed,(an( enzyme((guanyl(transferase)(adds(a(guanine(nucleotide( (7mG/7-methylguanosine)(to(the(end(of(the(newly(generated( pre-mRNA' o Easy(to(identify(cap( ( ' • As(elongation(proceeds,(Ser2’s(start(to(be(phosphorylated'by(( other(kinases.(This(allows(other(proteins(to(bind(such(as( splicing(factors( ( ( ' • During(elongation(the(phosphorylation(of(Ser5'is'gradually'lost,(and( proteins(involved(in(3’-end(processing(bind(to(the(CTD' ' ( TRANSCRIPTION'–'TERMINATION'(RNA'pol'II)' • The(termination(of(transcription(occurs(when(a(specific(sequence( motif((AATAAA)(occurs' • This(is(recognised(by(the(Cleavage(and(Polyadenylation(Specificity( Factor((CPSF)(&(Cleavage(Stimulation(Factor((CstF),(which(“ride”(on( the(CTD( ( ( ' • CPSF'&'CstF'transfer(to(the(mRNA(and(cause(cleavage'of'the' message' ' ' ' ' ' • Poly-A(Polymerase((PAP)(then(adds(multiple(As(to(create(the( polyA(tail' o The(Poly-A(Binding(Proteins((PABP)(bind(and(protect(it( ( ( ' • Finally,(more(As(are(added(to(achieve(a(particular(length(polyA(tail' o The(length(of(the(polyA(tail(is(important(for(stability(and( function(of(the(mRMA' '

93

( (

94 (

(

BIOM20001(MCB(

SPLICING' • Intron(are(defined(by(consensus(sequences' • Utilises(the(structure:(Spliceosome' ' Spliceosome' • Composed(of(snRNPs' o Ribonucleoprotein((complex(od(both(RNA( and(protein)' o RNAs(are(small(nuclear(RNAs((snRNAs)' • Specific(sequence(of(bases(recognised(by(the(spliceosome(in(order(to(cut' ( ( • Correct(reading(frame(is(imperative(because(without(it,( STOP(codons(are(common,(so(any(splicing(error(that( disrupts(the(reading(frame(can(pote...