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Delayed ripening and improved fruit processing quality in tomato by RNAi mediated silencing of three homologs of 1 aminopropane 1 carboxylate synthase gene

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Trong các tác nhân gây ra sư chín hóa sinh của thực vật, Ethylene được biết như một trong những nhân tố để bắt đầu, điều chỉnh và điều phối sự biểu hiện của hệ thống các Genes tham gia vào quá trình chín. Sự bùng nổ trong sản xuất ethylene là mốc quan trọng cho sự khởi đầu của chín của trái cây thời kỳ. Trong nghiên cứu này nhóm nghiên cứu đã cho thấy một kết quả kahr quan khi có thể kéo dài quá trình bản quản cà chua lên tớ 45 ngày mà không làm ảnh hưởng đến mùi vị và giá trị dinh dưỡng của cà chua.

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jou rn al h om ep a g e :w w w e l s e v i e r c o m / l o c a t e / j p l p h

Physiology

a Plant Polyamine, Transgenic and RNAi Research Laboratory, Department of Genetics, University of Delhi South Campus, New Delhi 110021, India

b Division of Post-Harvest Technology, Indian Agricultural Research Institute, New Delhi 110012, India

a r t i c l e i n f o

Article history:

Received 4 October 2012

Received in revised form 18 February 2013

Accepted 18 February 2013

Available online 16 March 2013

Keywords:

ACC synthase

Delayed ripening

Ethylene

Fruit quality

Polyamines

a b s t r a c t

Theripeninghormone,ethyleneisknowntoinitiate,modulateandco-ordinatetheexpressionof var-iousgenesinvolvedintheripeningprocess.Theburstinethyleneproductionisthekeyeventforthe onsetofripeninginclimactericfruits,includingtomatoes.Thereforeethyleneisheldaccountablefor thetonsofpost-harvestlossesduetoover-ripeningandsubsequentlyresultinginfruitrotting.Inthe presentinvestigation,delayedripeningtomatoesweregeneratedbysilencingthreehomologsof 1-aminocyclopropane-1-carboxylate(ACC)synthase(ACS)geneduringthecourseofripeningusingRNAi technology.ThechimericRNAi-ACSconstructdesignedtotargetACShomologs,effectivelyrepressedthe ethyleneproductionintomatofruits.Fruitsfromsuchlinesexhibiteddelayedripeningandextended shelflifefor∼45days,withimprovedjuicequality.Theethylenesuppressionbroughtabout composi-tionalchangesinthesefruitsbyenhancingpolyamine(PA)levels.Further,decreasedlevelsofethylene

inRNAi-ACSfruitshasledtothealteredlevelsofvariousripening-specifictranscripts,especiallythe up-regulationofPAbiosynthesisandascorbicacid(AsA)metabolismgenesanddown-regulationofcell wallhydrolyzingenzymegenes.Theseresultssuggestthatthedown-regulationofACShomologsusing RNAicanbeaneffectiveapproachforobtainingdelayedripeningwithlongershelflifeandanenhanced processingqualityoftomatofruits.Also,thechimericgenefusioncanbeusedasaneffectivedesignfor simultaneoussilencingofmorethanonegene.Theseobservationswouldbeusefulinbetter understand-ingoftheethyleneandPAsignalingduringfruitripeningandmolecularmechanismsunderlyingthe interactionofthesetwomoleculesinaffectingfruitqualitytraits

© 2013 Elsevier GmbH All rights reserved

Introduction

Tomatoisoneofthemostvaluablefruitcropacrosstheworld

andisrichinminerals,fibers,vitaminsandantioxidants(Rajam

etal.,2007).Italsoservesasamodelsystemforripeningrelated

studies.Tomatofruitripeningis initiatedwithclimactericburst

ofethylene,whichco-ordinates andregulatestheexpressionof

ripening-specificgenesinfruit(Osorioetal.,2011).The

biosyn-thesisofethylenestartswithS-adenosylmethionine(SAM),which

Abbreviations: ACC, 1-aminocyclopropane-1-carboxylic acid; ACS, ACC

syn-thase; ADC, arginine decarboxylase; NPT-II, neomycine phosphotransferase; ODC,

ornithine decarboxylase; PA, polyamine; PLW, physiological loss of water; Put,

putrescine; SAMDC, S-adenosylmethionine decarboxylase; Spd, spermidine; Spm,

spermine; TAs, titratable acids; TSS, total soluble solids; WT, wild-type.

∗ Corresponding author at: Department of Genetics, University of Delhi South

Campus, Benito Juarez Road, New Delhi 110021, India Tel.: +91 11 24110866;

fax: +91 11 24112437.

E-mail address: rajam.mv@gmail.com (M.V Rajam).

isconvertedinto1-aminocyclopropane-1-carboxylicacid(ACC)by ACCsynthase(ACS),andACCisfinallyconvertedintoethyleneby ACCoxidase(ACO)(AdamsandYang,1979).ACScarriesoutthe rate limiting stepin ethylene biosynthesis (Yang and Hoffman,

1984)anditintomato,is apartofmulti-genefamily, compris-ingninehomologs,whicharedifferentiallyexpressed(Caraand Giovannoni, 2008) ACS2 and ACS4 are responsible for climac-tericburstofethyleneproductionattheonsetofripening(termed System-2),whileACS1AandACS6maintainbasallevelsofethylene

ingreentissues(termedSystem-1)(Rottmannetal.,1991;Lincoln

etal.,1993).Ithasbeenreportedthatbasalethyleneisessential forprogressionofsystem2ethylene.Tomatofruitcanalso initi-atesystem2ethyleneindependentlyofsystem1,whichproves thatripening-associatedethylenebiosynthesisisregulatedbyboth auto-catalyticsystemandethylene-independentfactors(Yokotani

etal.,2009)

Anumber ofphysiologicaleffectsofethyleneinplants seem

tobeantagonizedbypolyamines[PAs:putrescine(Put), spermi-dine (Spd)and spermine (Spm)]by modulating genesinvolved 0176-1617/$ – see front matter © 2013 Elsevier GmbH All rights reserved.

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Fig 1. T-DNA map of RNAi-ACS binary vector Antisense chimera was designed to be 50 bp shorter than the sense chimera, such that after transcription the antisense RNA folds back and complements with sense RNA to form dsRNA molecules with loop in between.

intheethylenesignalingand biosyntheticpathways(Apelbaum

etal.,1981;Handaetal.,2011).IncreasedlevelsofPAshaveshown

toresultindelayedfruitripening,increasedfruitfirmness,

pro-longedshelflife,reducedethyleneandrespirationrateemissions

(Bregolietal.,2002;Nambeesanetal.,2010).Inplants,Putiseither

synthesized directly from ornithine via the action of ornithine

decarboxylase(ODC)orindirectlyfromarginineviaarginine

decar-boxylase(ADC).HigherPAs(SpdandSpm)aresynthesizedbythe

sequentialadditionofaminopropylgroupstoPutbySpdsynthase

(SPDSYN)andSpmsynthase(SPMSYN).Theaminopropylgroups

areprovidedfromdecarboxylatedS-adenosylmethionine(dcSAM)

whichisformedbydecarboxylationofSAMbySAM

decarboxyl-ase(SAMDC).SAMactsasthecommonprecursorforbothPAand

ethylenebiosynthesispathways,suggestingittobeaconstraintfor

eitherofthebiosyntheticpathway(Tiburcioetal.,1990)

Thegreentomatotransformsintoripefruitwhileit

accumu-latescarotenoidpigmentsandturnsred,developsflavorandaroma

withalterationinsugars,acidsandvolatileprofilewithsoft

tex-ture(Giovannoni,2001).Ripening-associatedsofteningisamajor

factor limiting fruitshelf life and storageand thus, contributes

tothetonsof lossesofthis crop.In fact,severalattempts have

beenmadetocontrolripeningprocess.Fordelayedripening,major

focushasbeenonthemanipulationofethyleneproduction,

per-ceptionandactionemployingeithersenseorantisensetechnology

(Hamiltonetal.,1990;Oelleretal.,1991;Theologisetal.,1993;

Yeetal.,1996;Wilkinsonetal.,1997;Xiongetal.,2003,2005)

Alltheseresearchershavebeensuccessfulinobtaininglow

ethyl-eneproducingtomatoes,displayinganextendedshelflifebutwith

compromisedfruitqualitytraits.However,selectivenatureofRNAi

canbemore specificfor suppressionand ismoreeffectivethan

eithersenseoranantisenseRNA(Fireetal.,1998).Additionally,

suppressionofmorethanonehomologwouldbemoreeffective

overshut-downofsinglehomolog.Fromtheperusalofliterature,it

isapparentthatPA-ethylenenexusplaysacrucialroleinfruit

ripen-ing.Thus,lookingatthemultifunctionalandregulatoryaspectsof

PAandethylene,itispossiblethatcontrolledmanipulationofthese

keyregulatorsratherthanstructuralorregulatorygeneoperating

ina singlebranchofbiosynthesis pathwaymayresultin better

improvementoffruitshelf lifeandqualitytraits.Inthepresent

study,inordertomodulatePA-ethylenelevels,wehavesuppressed

theexpressionofthreehomologsofACSgene(ACS6,ACS1Aand

ACS2),therebytargetingsystem1and 2productionofethylene

simultaneouslyattheonsetoffruitripening,usingRNAiapproach

Fruit-specificdown-regulationofthesegeneswasaccomplishedby

2A11promoterfromtomato

Materials and methods

Insilicoanalysis

Thenucleotidesequencesoffruit-specifichomologsofACS,viz.,

ACS6(GenBankID,AF179249),ACS1A(GenBankID,U18056.2)and

ACS2(GenBankID,NM001247249.1)fromSolanumlycopersicum

werecomparedbypair-wisealignment usingNCBIBLAST2Seq

ToavoidunintendedtargetingbyRNAiintransformedtomato,the selectedACShomologswereevaluatedfortheirprobableoff-target

insilico.Thecomplete mRNAsequences forallthree ACSgenes wereusedforhomologysearchingwithalltheavailablesequences

innrdatabaseusingNCBIBLAST.TheindividualmRNAsequences werealsocheckedforprobableoff-targetsbysplittingitinto21bp fragmentimitatingthe siRNA.The off-targetfree partialmRNA sequenceofACS6,ACS1AandACS2werechosenforpreparingRNAi construct.Theprimersequencesdesignedfortheamplificationof ACShomologs,2A11promoterandantisenseACS(Chimeric)are giveninTableS1

GenerationoftomatotransformantswithRNAi-ACS(chimera) construct

ThepartialcDNAofthreeACShomologsACS6(201bp),ACS1A (286bp) and ACS2 (506bp) were amplified from tomato (fruit pericarp) total RNA by semi-quantitative RT-PCR using specific set of primers designed with restrictionsites ACS1A and ACS2 wereclonedintopBSKvectorsequentiallyusingKpnI–EcoRIand EcoRI–BamHI restriction sites respectively The 2A11 promoter (1.35kb–GenBankID,DQ453963)wasisolatedfromtomatoand clonedintopGEM-Teasy.Followingsequencing,2A11promoter wasexcisedbyEcoRIandSacIandligatedintopCAMBIA2300binary vector.ACS6wasclonedin pCAMBIA2300downstream to2A11 promoter usingSacIand KpnIrestrictionsitesfollowedby liga-tionofACS1A+2(frompBSK)withKpnIandBamHIrestrictionsites SenseACS6+ACS1A+ACS2wasusedasatemplateinPCRreaction

toamplifyanantisensechimera,whichis50bpshorterthanthe senseone.ItwasclonedintopCAMBIA2300binaryvector harbor-ing2A11promoter,polyAsignalandsenseACS6+1A+2byusing BamHIandXbaIrestrictionsites.ThepolyAsignalfrompRT101 vec-torwasalsoclonedintopCAMBIA2300vectorusingXbaIandPstI restrictionsites(Fig.1).RNAi-ACSconstructwasmobilizedinto AgrobacteriumtumefaciensLBA4404strainbychemical transforma-tion,andwasthenutilizedtotransformcotyledonsoftomato(S lycopersicumMill.cv.PusaEarlyDwarf)byaproceduredescribed

byMadhulathaetal.(2007) GenomicDNAisolationandtransgeneintegrationintomato transformants

GenomicDNAwasisolatedfromtheleavesofwild-type(WT) andtransformantsusingCTABmethod(Doyleand Doyle,1990) The transformants were screened by PCR for the presence of transgene.Primerpairsfortheamplificationof750bpfragment

ofNPT-IIgeneareF,5-TCAGAAGAACTCGTCAAGAA-3 and R,5 -ATGGGGATTGAACAAGATGG-3

GenomicDNA(10␮g)wasdigestedwithEcoRIenzymeand sub-jectedtoDNAhybridizationtoconfirmtheintegrationandcopy numberoftransgeneusingradiolabeledNPT-IIgeneprobe.Blots werepreparedbystandardprotocol(Sambrooketal.,1989)using

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primerkitfollowing themanufacturer’sguidelines(BRIT,India)

Pre-hybridizationandhybridizationwerecarriedoutasdescribed

bySambrooketal.(1989)

AtotalofthirtyRNAi-ACS(chimeric)transformants,confirmed

fortransgeneintegrationbyPCRandDNAhybridization(Fig.S2)

weremaintainedbothintransgenicgreen-house/net-house

condi-tions

Expressionanalysis

Pericarp tissue (50mg) of mature green (MG), breaker red

(BR), pink red (PR) and red ripe (RR) fruit was pulverized to

homogenate powder The homogenate was used for isolation

of total RNA according to the manufacturer’s guidelines with

TriZol reagent (Invitrogen, USA) with subsequent RNase free

DNase(Fermentas,Canada)treatmenttoremoveanyDNA

con-tamination Semi-quantitative RT-PCR was performed to check

transcriptlevelsofthetargetgeneandvariousgenesinvolvedin

fruitripening,inRNAi-ACSandWTtomatoplants.DNA-freeRNA

(200ng)wasthenusedforone-stepRT-PCRreactionbyfollowing

themanufacturer’sguidelines(Taurus-Scientific,India).The

prod-ucts wereanalyzed on ethidiumbromide stained 1.5% agarose

gel.Primersusedinthestudyweredesigned withreferenceto

nucleotide sequences registered in the Genbank database The

reactionconditionswereasfollows:45◦Cfor50min,followedby

94◦Cfor5min,ncyclesof94◦Cfor30s,annealingtemperature

for30sand72◦Cfor30s,finalextensionat72◦Cfor15min.All

semi-quantitative-RT-PCR experiments were carried out thrice

in three independentexperiments by using the pulverized

tis-sue of three fruits (at same stage) from same plant (pooled)

The results presented are relative The accession numbers for

ripening-associated genes selected for transcript analysis are:

ornithine decarboxylase (SlODC, NM001247687.1), arginine

decarboxylase(SlADC1,NM001247135.1),S-adenosylmethionine

decarboxylase(SlSAMDC1,EU196515.1;SlSAMDC2,EU196516.1;

SlSAMDC3, EU196517.1), spermidine synthase (SlSPDSYN,

NM001247564.1), ACS6 (AF179249), SlACS1A (U18056.2),

SlACS2 (NM001247249.1), SlACS4 (NM001247351), SlACO1

(NM001247095), SlE8 (X13437.1),

1-deoxy-d-xylulose-5-phosphate synthase (SlDXS1, AF143812), (SlPSY1, EF157835.1),

lycopene-epsiloncyclase(SlLES,Y14387),SlTAGL1(AY098735.2),

polygalacturonase (SlPG, X05656), expansin (SlEXP1, U82123),

␤-galactosidase4(SlTBG4,AF020390),␣-xyloglucan

endotransglu-cosylase/hydrolase (SlXTH5, AY497475), l-galactono-1,4-lactone

dehydrogenase (SlGLDH, NM001247674.1), ascorbate oxidase

(SlAO, AY971876.1), dehydroascorbate reductases (SLDHAR1,

AY971873.1;SLDHAR2,AY971874;SlMDHAR,NM001247084.1)

andactin(SlActin,BT012695).Thedetailsofprimersareprovided

inTableS2

IsolationofsmallRNAsandRNAhybridizationfordetectionof

siRNAsinRNAi-ACStomatolines

TotalRNA (200–400␮g)fromBR fruitwasenriched for low

molecularweightRNAasperthemethoddescribedbyLuetal

(2007).About90␮gofthelowmolecularweightRNAwas

frac-tionatedtoseparatesmallRNAs(20–25nt)using15%denaturing

polyacrylamidegel accordingto Luet al.(2007) RNAfractions

wereelectroblottedontothepositivelychargednylonmembrane

(MDI,India)usingsemi-dryblot(BenchtopLabsystems,India)and

the membrane was incubated for overnight at 42◦C in a

pre-hybridization buffer(Sambrook etal., 1989).Hybridization was

carriedoutat36◦Cfor20husingradiolabeledACS1A,ACS2and

ACS6DNAasprobe

Estimationofrateofethyleneproductionintomatofruits Threeredfruitswereenclosedin100mLofanair-tightcontainer for1hatroomtemperature.Theheadspaceatmosphere(3mL)of thecontainerwaswithdrawnandinjectedintogaschromatograph (HP5890,HewlettPackard,USA)forethyleneestimation(Singh andPal,2008).Theexperimentwascarriedoutthricewithtwenty replicatesineach

Measurementofrespiratoryactivityintomatofruits Theindividualfruitsweresealedinanair-tightcontainerfor

1h.Respiratoryactivityoftheharvestedfruitswasdeterminedby headspacegasanalysisofjarusingCO2/O2 analyzer(Checkmate

9900O2/CO2,PBIDansensor,Denmark)(SinghandPal,2008).The experimentwascarriedoutthricewithtwentyreplicateseach Determinationofphysiologicallossofwater(PLW)

PLWinRRfruitsduringfirsttendaysoftheirstorage(atroom temperature)wasestimatedby subtractingthesampleweights fromtheirpreviousrecordedweightsandwasrepresentedas% PLW/day comparedtotheinitialweight.Data wasrecordedfor twentybiologicalreplicateseachinthreeindependentsets Polyamineanalysis

About100mgofpericarptissue(fromdifferentstagesoffruit ripening,viz.,BRandRRstages)washomogenizedin1mLof10% perchloricacid Thehomogenateofthreefruits(withsameage, fromsameplant)waspooled.Theextractwasfractionated, dan-sylated,chromatographedandquantifiedbythemethoddescribed

byBajajandRajam(1996)usingdualwavelengthfluorometer (Bio-Rad,VersaFluor,USA)withanexcitationwavelengthof350nmand

anemission wavelengthof495nm.ThePolyaminecontentwas estimatedinthreefruitseachinthreeindependentexperiments Determinationofon-vineripeningperiod

Flowersweretaggedatanthesisanddayswerenotedforfruit formationinthreeindependentsetswithtwentyreplicatesineach

MGfruitsdisplayingfirstsignofcolorchangewereidentifiedas

BRstage.DaysforBRtoreachRRwerenotedforRNAi-ACS,WT andunrelated(UR)controlfruitstodeterminetheon-vineripening period

Determinationoffruitshelflife

RR fruits(twentyreplicates) ofRNAi-ACS,WTandURplants werekeptatroomtemperatureandtimewasnotedforvisualsigns

ofshriveling.Theexperimentwascarriedoutthrice

Measurementoftotalsolublesolids(TSS)content Tomatofruit(RRstage)homogenatewasutilizedformeasuring TSScontentbyahandrefractrometer(model:Fisher,Japan)(Singh andPal,2008).Thehomogenateofthreefruits(fromsameplant) waspooled.TSScontentwasmeasuredinninefruitseachinthree independentexperiments

Estimationoftitratableacidity The homogenate of three fruits(RR stage)from same plant werepooled.Totaltitratableacidity(TA)wasthendeterminedby titratingthehomogenateagainst0.1NNaOHsolutionusing phe-nolphthaleinasanindicatortotheendpointatpH8.1(Singhand

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experiments

Determinationofascorbicacid(AsA)content

AsAcontentintomatofruitsatRRstagewasestimated

titrime-tricallyusing2,6-dichlorophenolindophenolasanindicatordye

AsAstandardwaspreparedbydissolving100mgofl-AsAin100mL

of1%HPO3(SinghandPal,2008).Thepooledhomogenateofthree

fruits(fromsameplant)wasutilizedfortheestimation.AsAcontent

wasmeasuredinninefruitsinthreeindependentexperiments

Quantificationoflycopenecontent

Lycopene fractions of the homogenized pericarp tissue (RR

stage) were determined using spectrophotometric method as

describedbyAOAC(2000).Thepooledhomogenateofthreefruits

(from same plant) were utilized in each experiment Lycopene

fractionswereestimatedinninefruitsinthreeindependent

exper-iments

Dataanalysis

Allresultswereobtainedfromatleastthreeindependent

exper-iments.Datapresentedareaverage(mean)withthestandarderror

fromalltheexperimentsandsignificantdifferenceswere

deter-minedbyStudent’st-test(P<0.05)

Results and discussion

ThreehomologsofACS,viz.,ACS1A,ACS2,andACS6were

consid-eredintandemforRNAi-mediateddown-regulationtoeliminate

anyredundancyassociatedwithgenefunctionandtoachieve

maxi-mumsuppressionoftheautocatalyticburstinethyleneproduction

However,ACS4wasnotconsideredforpresentstudyduetothe

unavailabilityofanyoff-targetfreeregionanditshomologywith

othertomato geneslikeexpansin(datanotshown).Toalleviate

thepleiotropiceffectswhichmightariseduetoconstitutive

down-regulationofethylene,fruit-specificexpressionofRNAi-ACSwas

achievedby2A11promoter(Fig.1).Thispromotershowslow

lev-elsofactivitythroughoutfruitdevelopmentbutgetsinducedto

highactivityattheonsetofripening(Pearetal.,1989).Previous

experimentsinourlabhaveshownthattomatoplantstransformed

with2A11-GUSconstructexhibitedGUSexpressionexclusivelyin

ripeningfruitwithpronouncedactivityinpericarp,vascular

bun-dles,placentaltissue andseedtegument(Fig.S1) Theseresults

werealsosupportedbydataobtainedbyLinetal.(2006)

EthylenesuppressioninRNAi-ACSfruits

FruitsfromallthirtyRNAi-ACStomatolinesalongwith

unre-latedcontrol(UR,otherRNAilinesfromlab)andWTplantswere

analyzedforrateofethyleneevolution.ResultspresentedinFig.2

showthatfruitsfromRNAi-ACSlinesliberatedreducedlevelsof

ethylene.EthyleneliberationwasfoundtobeleastinRNAi-ACS60

andRNAi-ACS81,releasingonly4–5%whencomparedwith

con-trols(WTandUR).FruitsofotherRNAi-ACSlinesshowed10–70%

ofethyleneevolutiontothat ofcontrolfruits.Thisdifferencein

ethyleneevolutionamongRNAi-ACSlinescouldbeattributedto

variablesuppressionofthetargetgene.Thisinturnisascribableto

differentialabundanceoftheintroduceddsRNA,asinfluencedby

siteofintegrationanddosageeffectoftheintroducedgenes(Fig

S2B)(Kohlietal.,2003;Kerschenetal.,2004)

Transcriptlevelsofthetargetedhomologs,viz.,ACS1A,ACS2and

ACS6,werecheckedbysemi-quantitativeRT-PCR.Resultsshowed

thatlevelsofACS2transcriptsinWTfruitswerehighthroughMG

toPRstageand declineddramaticallyatRRstage(Fig.3A).The observeddeclineinACStranscriptsiscollinearwiththeonsetof 2A11promoteractivity.RNAi-ACSlinesreleasinglowlevelsof eth-ylene,displayeddrasticreductioninACS2transcriptlevels.This declineintranscriptlevelswasmorepronouncedinRNAi-ACS81 lineatallripeningstagesandsubtledinRNAi-ACS123and RNAi-ACS125 In WT tomato, ACS1A and ACS6 transcript levels were substantiallylowerthanACS2mRNAlevels(asweredetectedinWT tomatoeswith30cyclesofamplificationincontrastto25cyclesfor ACS2).Previously,itwasreportedthattheexpressionofACS6and ACS1Agenesisrestrictedtotheearlyfruitdevelopmentalstages (Nakatsukaetal.,1998;Barryetal.,2000),butourresultsrevealed thattheACS1AandACS6transcriptspersistedthroughMGtoRR stageinWTtomatoes.InRNAi-ACStomatolines,theexpression

ofACS6andACS1AgenesfollowedthesametrendasthatofACS2 Theseresultsshowedacorrelationbetweentranscriptabundance andrateofethyleneevolutioninRNAi-ACSfruits

siRNAsspecifictoACS1A,ACS6andACS2weredetectedatBR stageinfruitsofRNAi-ACSlines.RNAi-ACS81linehasexhibited highlevelsofsiRNAswithundetectablelevelsoftranscriptsofall thetargetedgenes(Fig.3B).Hence,declineinACStranscriptsin RNAi-ACSfruitsexpressingdsRNAisanRNAimanifestation

OnthebasisofRT-PCRandsiRNAdetectionresults,RNAi-ACS lineswerecategorizedintohighlysilencedlines(RNAi-ACS60and RNAi-ACS81) and moderately silenced lines (RNAi-ACS123 and RNAi-ACS125).RNAi-ACS81andRNAi-ACS123displayinghighand moderatesilencing,alongwithWTwereutilizedforfurtherwork

ontheexpressionanalysisofripening-relatedgenes.Declinein transcriptslevelsofACS4,ACO1andE8wasnotedincaseofboth theRNAi-ACSlinesstudied,overWTfruits(Fig.3C).Aplausible explanationtothisobservationisthepositivefeedbackregulation

ofthesegenesbyethylene(Barryetal.,1996;Nakatsukaetal.,

1998).DeclineinACS4geneexpressionmaynotbesolelyduetothe ethyleneregulation,itmightalsobeduetothesharedhomology betweenACS2andACS4genesequenceswhichcouldhavecaused theoff-targetingofACS4gene.Moreover,conversionofSAMtoACC

byACCsynthasemarkstheratelimitingstepforethylene biosyn-thesiswhichpossiblyexplainsthatACSgenerepressionhasleadto lowlevelsofACO1transcriptsinRNAi-ACS81line.Transcriptionof E8infruithasbeenshowntoberegulatedandstimulatedby eth-ylene,whichiswellevidentbythepresenceofethyleneregulated sequencesinE8genepromoter(Deikmanetal.,1998).TAGL1codes fortranscriptionfactor,whichactivatesethylenebiosynthesisby bindingtoACS2promoter(Vrebalovetal.,2009).Theexpressionof thisgenewasanalyzedandwecouldnotseeanysignificant differ-enceinTAGL1transcriptaccumulationinfruitsofRNAi-ACSlines overWT,suggestingthatalterationsinethylenelevelsinRNAifruits didnotaffecttheexpressionofthisgene(Fig.3C)

PolyamineaccumulationinRNAi-ACSlinesoftomatowith reducedethylenelevels

InWTtomatofruitsatBRandRRstagesofripening,Putlevels werefoundtobehighestamongthreePAsfollowedbySpdandSpm titers.PutandSpmweremainlypresentinfreefractionsfollowed

byconjugatedandboundforms.ButSpdpoolsweremaintained

byalmostequalfractionsoffreeandconjugatedformsfollowedby boundform.AsthefruitattainsRRstage,PAlevelswerereducedto almosthalfoftheinitiallevelsatBRstage(Fig.4).RNAifruitsatBR stageexhibited13–25%increaseinPut,15–40%increaseinSpdand 15–45%increaseinSpmoverWT.IncontrasttoWTRRtomatoes, RNAi-ACS81tomatoshowedhigherlevelsofPAsatRRthanatBR, with100%increaseinPutand150%increaseinSpdandSpmlevels ExpressionpatternofODCandADCgenesdidnotalter,while SAMDC1andSPDSYNmRNAlevelswereincreasedinboth RNAi-ACS81andRNAi-ACS123fruitsoverWT(Fig.5).Therewasalso

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Fig 2. Ethylene levels in fruits of RNAi-ACS lines and controls Bars represent the means of twenty biological replicates and three independent experiments, with standard error values as error bars * Significant at P < 0.05 between controls and RNAi lines.

no change in transcript levels of SAMDC2 and SAMDC3 genes

Thesetwo homologsexhibited differentialtranscript

accumula-tion,with SAMDC2 mRNAlevelsbeing higher in BRstage than

RR,whileSAMDC3transcripts,althoughdetectedinBRstage

van-ishedatRRstage.Interestingly,transcriptlevelsofSAMDC2and

SAMDC3werefoundtobelowerthanSAMDC1mRNAlevels.Thus,

SAMDC1seemstobepredominantlyresponsibleforSAMDC

activ-ityinripeningfruits.TheincreasedaccumulationofSAMDC1and

SPDSYNtranscriptswasthereforeaccountableforenhanced Spd

andSpmcontentinRNAi-ACSfruits.ElevatedSAMDCandSPDSYN

transcriptsaccumulationinturnmaybebecauseofdiversionof SAMpoolstowardPAbiosyntheticpathway(duetoreductionin ethylenebiosynthesis).Henceforth,wehypothesizeapositive feed-backregulationofSAMDCandSPDSYNgenetranscriptionbytheir upstreamprecursor,i.e.,SAM,whichisalsosupportedbythe exper-imentscarriedoutinourlab,i.e.,asignificantdecreaseinethylene productionwasobservedwithover-expressionofPAbiosynthesis genesduringfruitripening(unpublishedresults).Thus,inresponse

tohigher availabilityof precursor(SAM), PA biosynthesis path-wayisactivatedcausinghigheraccumulationofSpdandSpm.The

Fig 3.Expression pattern of ethylene biosynthesis and related genes in tomato fruit during ripening (A) Semi-quantitative RT-PCR analysis of ACS transcript levels in WT and RNAi-ACS tomato lines at different stages of fruit ripening; (B) detection of ACS specific siRNAs in RNAi-ACS transformants by modified RNA hybridization; (C) semi-quantitative RT-PCR analysis for expression of ethylene biosynthesis and related genes, at BR and RR stages of fruit ripening ‘n’ denote no of cycles in semi-quantitative RT-PCR analysis.

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*† *†

*† *†

*†

*†

RNAi-ACS li nes

Free Con j Boun d

Fig 4.The levels of free, conjugated and bound PAs in WT and RNAi-ACS tomato

fruits Bars represent the means of three biological replicates and three independent

experiments, with standard error values as error bars *,†, ‡as Significant differences

in free, conjugated and bound PAs, respectively at P < 0.05 as compared to their

respective controls.

increaseinPutamountinfruitsofRNAi-ACSlinescanbedueto

theenhancedinter-conversionofexcesspoolsofhigherPAs,viz.,

Spd/SpmtoPutthroughacetylationmechanismbySpd/Spm

N1-acetyltransferase‘SSAT’(Seiler,2004;HazarikaandRajam,2011)

Ourdataindicatesthatinterferencewithethylenebiosynthesis

intomatofruitsofRNAi-ACSlineshadresultedintheaccumulation

ofPAsinsuchfruits,whichsupportsthecompetitiveinteraction

betweenethyleneandPAbiosyntheticpathways

DelayedripeningandenhancedshelflifeoffruitsinRNAi-ACS

linesoftomato

Reductioninethylenelevelshasledtosignificantreductionin

CO2 evolution(markerforrespiration)inRNAi-ACStomatolines

overcontrols(WTandUR).Amongthevariouslinesanalyzedfor

rateofrespiration,RNAi-ACS60 andRNAi-ACS81 werefoundto

exhibit∼50%reductioninrespiratoryactivityinharvestedfruits

overcontrolfruits,whilerestoftheRNAi-ACSlinesshowedupto

30%reductioninrateofrespiration(Table1).Thevariationin

respi-ratoryactivityofdifferentfruitscorrespondstothedifferentlevels

ofethyleneliberatedbysuchfruits.Theresultsareinaccordance

withtheobservationsmadebyDefilippietal.(2004)inappleand

Wangetal.(2010)intomato.Resultsonphysiologicallossofwater

(PLW)showedalmostsimilartrendsofreducedPLWpercentage

amongtheRNAi-ACStomatoesoverWTfruits(Table1).The

reduc-tionwasprominentwithupto40%reductionintherateofPLWin

RNAi-ACStomatoesovercontrols.Suchareductioninrespiratory

activity,PLWandthusslowermetabolicratehasdelayedripening

andextendedtheshelflifeofRNAi-ACStomatofruits

AsignificantdelayofonvineripeningforRNAi-ACStomatoes

wasrecordedascomparedtocontrolfruits.Onvineripeningperiod

(BRtoRR)wasdelayedfor∼45daysinRNAi-ACS60 and

RNAi-ACS81overcontrols(Table1).RRfruitsharvestedfromcontrols

andRNAi-ACSlinesshowedsignificantdifferenceintheirshelflife

understoragecondition(roomtemperature).Controlfruitskept

atroomtemperaturestartedrotting after8–10days ofharvest,

whilemostpromisingRNAi-ACSlinesshowedextendedshelflife

ofabout45daysbeyondnormalshelflifebeforedecaying(Table1;

Fig.6A).Guillénetal.(2007)havedemonstratedasimilar

corre-lationbetweendegreeofethyleneinhibitionandrateofripening

withdose-andtime-dependentapplicationof1-MCPintomato

Fig 5.Semi-quantitative RT-PCR analysis for expression of PA biosynthesis genes

in WT and RNAi-ACS81 and RNAi-ACS123 fruits ‘n’ represents no of cycles in semi-quantitative RT-PCR analysis.

Cell wall componentsincluding cellulose, hemicelluloseand pectin arethe majorcontributors for flesh firmnessand hence the shelf life During ripening, cell wall undergoes substan-tialdisassembly caused by increasedexpression of various cell walldegradingenzymeslikepolysaccharidehydrolases/glycoside hydrolase, transglycosylases, lyases and expansins (Brummell,

2006).EXP1,TBG4,PG and XTH5geneshave been shownto be specificallyexpressedduringfruitripeningandplaymajorrolein fruitsoftening(Pirrelloetal.,2009).Here,comparativeexpression analysisofgenesinvolvedincellwallhydrolysisindicated consid-erablereductionintranscriptsofEXP1,TBG4,PGandXTH5genes duringfruitripeninginRNAi-ACSlinesover WTfruits(Fig.6B) Thiscouldbeduetothereducedethylenelevelsinthese toma-toesasexpressionofthesegeneshasbeenreportedtobeethylene responsive(MaclachlanandBrady,1994;SmithandGross,2000; Zhaohuietal.,2009).InRNAi-ACSlines,theinhibitionofEXP1,TBG,

PGandXTHexpressionisconsistentwiththedelayoffruitripening andprolongedshelflifeoffruitsinfluencedbyreductionin ethyl-enelevels.Thus,declineinrespiratoryactivityandlowertranscript abundanceofcellwalldegradinggeneshasledtothedelayed ripen-ingandenhancedshelflifeinRNAi-ACStomatolines.Inaddition, increasedPAaccumulationinfruitsofRNAi-ACSlinesmayhavealso influencedtheenhancedshelflifepossiblybystabilizingthe mem-branes.PAshavebeenreportedasmodulatorofsupra-molecular conformationofpectin.EvidencesareavailablesupportingthatPA canboundcovalentlywithcellwallandinhibitionofPA biosyn-thesisinterfereswithcellwallformationmakingitamorphousand itsexogenousapplicationreversesthechanges(Bertaetal.,1997; Messiaenetal.,1997)

ImprovedfruitqualityinRNAi-ACStomatolines Totalsolublesolids(TSS)andtitratableacids(TAs)areofspecial significanceforprocessingindustry.TSSofaproducecomprisesof sugar,mineralandacidcontentsandreflectsitsspecificgravityor density.ItwashighlyencouragingtoobservethatRNAi-ACS toma-toesreleasingtracesofethylenerecordedveryhighlevelofTSS with∼40–45%increase(Table2).Althoughpreviousreports(Opiyo andYing,2005)havesuggestedTSStobeethyleneindependentbut ourresultsindicateacorrelationbetweenaccumulationofTSSand ethylenereduction,andtheunderlyingmechanismforthisstillto

beworkedout

Trang 7

Table 1

Storage attributes of fruits from control and RNAi-ACS lines of tomato.

RNAi lines Respiration rate/CO 2 (nL/g fresh wt./h) PLW (%/day) On vine ripening (days) Shelf life (days)

RNAi-ACS60 4.12 ± 0.31 * 0.48 ± 0.09 * 56.66 ± 0.72 * 53.72 ± 0.93 *

Data is the mean ± standard error, based on at least three independent experiments with twenty replicates in each experiment.

* Significant at P < 0.05 between controls and RNAi lines.

RNAi-ACSfruitswerefoundtobear∼1.5–2.0foldincreasein

TAsover controls(Table2).Lower rateof respiration in

RNAi-ACS fruits explains higher accumulation of TAs in these fruits,

since organic acids (e.g citric acid) have been established as

substrates of respiration, and is an ethylene-dependent factor

(Defilippietal.,2004).ThehigherlevelsofTSSwithsimultaneous

increaseinTAsmightprovideacharacteristicflavorforRNAi-ACS

fruits

Inplantcells,ascorbicacid(AsA)iscontinuouslyoxidizedand

reducedwhereascorbicfreeradicalsanddehydroascorbate(DHA)

are the oxidation products, which can be reconverted back to

AsA.Ascorbatehasbeenestablishedasanimportantco-factorfor

invitroactivityofACO(Smithetal.,1992).Asageneraltrend,it

hasbeenseenthatAsAlevelsdeclineduringripeningand

senes-cence,andhasbeencorrelatedwithitsconsumptioninethylene

biosynthesispathway.Althoughinourcase comparablelevelof

AsAwasnotedinallRNAi-ACSlinesscreened(Table2 inspiteof

theblockageofethylenebiosynthesispathway.GLDHoxidizes

L-galactono-1,4-lactonetoAsA.DHAR1,DHAR2,MDHARandAOare

involvedinAsAoxidationandrecycling(Stevensetal.,2007).When

transcript profile of genes involved in AsA biosynthesis and recyclingpathwaywasanalyzed,GLDH1andAOgenesshowedan enhancedexpressionatBRstagewhiletheothergenes,viz.,DHAR1, DHAR2,MDHARwereunalteredintheirexpressionpattern(Fig.7) Theup-regulatedexpressionofbothbiosyntheticaswellas oxida-tiongenes,maintainsAsApoolsinRNAi-ACStomatofruitsandalso pointstowardtheirregulationbyethylene

DecreaseinlycopenecontentinRNAi-ACSlinesoftomato Lycopenecontentshowedsignificantreductioninitslevelsin

RRfruitsofRNAi-ACSlinesovercontrols,rangingfrom10to40% reduction (Table 3) Fruitsfrom RNAi-ACS lines – RNAi-ACS60, RNAi-ACS81andRNAi-ACS71.2,releasingtracesofethylene exhib-itedlightredcolorevenafter∼70daysoftheirharvest(atBRstage) Tomatoesfromtheselinesdisplayed∼40%reducedlycopene con-tentoverthecontrols.Expressionpatternoflycopenebiosynthesis gene,PSY1showedsignificantreductionintranscriptlevelinBRand

RRstagesoffruitripeningwhileDXS1andLESwhichisinvolvedin catabolismoflycopene,showednosignificantdifferencefromthat

Fig 6.Storage attributes of tomato fruits from controls and RNAi-ACS lines (A) Demonstration of extended shelf-life of RNAi-ACS tomatoes at room temperature after 70

Trang 8

Table 2

Fruit quality traits in control and RNAi-ACS lines of tomato.

RNAi lines TA (g/100 g) AsA (mg/100 g) TSS ( ◦ BRIX)

Wild-type 0.42 ± 0.08 27.97 ± 0.84 5.62 ± 0.13

Unrelated control 0.39 ± 0.19 27.13 ± 0.76 5.44 ± 0.50

RNAi-ACS60 0.97 ± 0.13 * 26.35 ± 1.32 8.03 ± 0.19 *

RNAi-ACS71.2 0.94 ± 0.10 * 27.21 ± 1.32 7.06 ± 0.18 *

RNAi-ACS123 0.81 ± 0.13 * 30.26 ± 1.60 7.77 ± 0.19 *

RNAi-ACS128 0.73 ± 0.11 * 26.86 ± 1.04 6.98 ± 0.59 *

RNAi-ACS109 0.72 ± 0.10 * 25.88 ± 0.75 7.31 ± 0.63 *

RNAi-ACS124 0.73 ± 0.09 * 29.13 ± 0.86 7.08 ± 0.51 *

Data is the mean ± standard error, based on at least three independent experiments

with nine replicates in each experiment.

* Significant at P < 0.05 between controls and RNAi lines.

Fig 7.Expression profile analysis of ascorbic acid biosynthesis and recycling genes.

‘n’ represents no of cycles in semi-quantitative RT-PCR analysis.

ofWTintermsoftheirmRNAlevels(Fig.8).Reductioninlycopene

contentinfruitsofRNAi-ACSlinesovercontrolscanbeattributed

toreducedPSY1mRNAlevels,whichispossiblyamanifestationof

adropinethylenereleaseshownbytheseRNAi-ACSlines

Fig 8.Expression profile of lycopene metabolic genes ‘n’ represents no of cycles

Lycopene content in control and RNAi-ACS fruits.

RNAi lines Lycopene (mg/100 g)

Unrelated control 10.04 ± 1.34 RNAi-ACS1A 4.80 ± 0.13 *

Data is the mean ± standard error, based on at least three independent experiments with nine replicates in each experiment.

* Significant at P < 0.05 between controls and RNAi lines.

Acknowledgements

Thisworkwasgenerouslysupportedbyagrantfrom Depart-mentofBiotechnology(BT/PR8657/PBD/16/738/2007),NewDelhi SeniorResearchFellowshiptoAartiGuptabytheCouncilof Sci-entificandIndustrial Research,NewDelhiisacknowledged.We alsothankUniversityGrantsCommissionforSpecialAssistant Pro-gramandDepartmentofScienceandTechnology,NewDelhifor FISTprogram

Appendix A Supplementary data

Supplementary data associated with this article can be found, intheonlineversion,at http://dx.doi.org/10.1016/j.jplph 2013.02.003

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