SignsthatRNAmightbemoreversatilecameintheearly1990s,whenbiologistsdeterminedthatsomesmallRNAscouldquashtheexpressionofvariousgenesinplantand,later,animalcells.Buttheydidn’tappreciatethemolecules’truepowersuntil1998.That’swhenAndrewFireoftheCarnegieInstitutionofWashingtoninBaltimore,Maryland,CraigMellooftheUniversityofMassachusettsMedicalSchoolinWorcester,andtheircolleaguesinjectedstretchesofdouble-strandedRNAintoworms.Double-strandedRNAformswhenafamiliarsinglestrandkinksbackinahairpinbend,puttingtwocomplementarysequencesalongsideeachother.Totheresearchers’surprise,double-strandedRNAdramaticallyinhibitedgenesthathadhelpedgeneratetheRNAinthefirstplace.Thisinhibition,whichwaslaterseeninfliesandotherorganisms,cametobeknownasRNAinterference(RNAi).IthelpedprovethatRNAmoleculeswerebehindsomegenesilencing.

Acomprehensivelistofpapers,labs,andotherresourcesfocusedonRNAi,providedbyOrbigen,Inc.

SubstantialcollectionofWeblinkstoanarrayofRNA-relatedresources,fromdatabasestotutorials;maintainedbytheInstituteofMolecularBiotechnology,Jena.

Fordecades,RNAmoleculesweredismissedaslittlemorethandrones,takingordersfromDNAandconvertinggeneticinformationintoproteins.ButastringofrecentdiscoveriesindicatesthataclassofRNAmoleculescalledsmallRNAsoperatemanyofthecell’scontrols.TheycanturnthetablesonDNA,shuttingdowngenesoralteringtheirlevelsofexpression.Remarkably,insomespecies,truncatedRNAmoleculesliterallyshapegenomes,carvingoutchunkstokeepanddiscardingothers.ThereareevenhintsthatcertainsmallRNAsmighthelpchartacell’sdestinybydirectinggenestoturnonoroffduringdevelopment,whichcouldhaveprofoundimplicationsforcoaxingcellstoformonetypeoftissueoranother.Sciencehailstheseelectrifyingdiscoveries,whicharepromptingbiologiststooverhaultheirvisionofthecellanditsevolution,as2002′sBreakthroughoftheYear.

Theyear’smoststunningrevelationsemergedinthefall,infourpapersexamininghowRNAinterferencehelpspilotapeculiar–andpervasive–geneticphenomenonknownasepigenetics.EpigeneticsreferstochangesingeneexpressionthatpersistacrossatleastonegenerationbutarenotcausedbychangesintheDNAcode.

Justwhenscientiststhoughttheyhaddecipheredtherolesplayedbythecell’sleadingactors,afamiliarperformerhasturnedupinastunningvarietyofguises.RNA,longupstagedbyitsmoreglamoroussibling,DNA,isturningouttohavestarqualitiesofitsown.

ResearchersarealsoprobingRNAi’spossibleroleindevelopmentanddisease.RNAihasbeenimplicatedinguidingmeristems,theplantversionofstemcells,sosomebiologistsbelievethatitmighthelpestablishthepathtakenbyhumanandothermammalianstemcellsastheydifferentiateintocertaintissues.Ifso,RNAicouldproveanessentialtoolinmanipulatingstemcells.AndifsmallRNAsinfluencecelldivisioninhumansastheydoinyeastandTetrahymena,minordisruptionsinthemachinerycouldleadtocancer.

ThetwosetsofexperimentsmighthelpexplainwhysmallRNAsexistinthefirstplace.InboththeyeastandTetrahymena,smallRNAs’freneticactivityisfocusedongenomeregions,suchascentromeres,thatcontainrepetitiveDNAresultingfromtransposons.TransposonsarebitsofDNAthatcanjumparoundthegenomeandinsertthemselvesatdifferentlocales;attimes,theyjamtranscriptionmachineryandcausedisease.Itappearspossible–althoughstilllargelyhypothetical–thatsmallRNAsevolvedveryearlyinlife’shistorytohelpprotectthegenomeagainstinstability.

InterestingdiscussionofRNAi,onWebsitedevelopedtoaccompanytextbookbyS.F.Gilbert.

Thisisjustoneofmanyareasthatremaintobeexplored.Researchersarestilltryingtosortouthowthewellover100differentmiRNAsfunctionandwhichspeciescontainwhichones.Therearehintsthattheybehavedifferentlyinplantsandanimals.AndsomerecentworksuggeststhatmiRNAsexertmorecontrolovergeneexpressionthanpreviouslybelieved.Alsoafocusofresearcharetheproteins,suchasDicer,thatarecriticalcogsintheRNAimachinery.

Thatnewscamefromseveralindependentgroups.Inonecase,ShivGrewal,RobertMartienssen,andtheircolleaguesatColdSpringHarborLaboratorycomparedfissionyeastcellslackingRNAimachinerywithnormalcells.Whenyeastcellsdivide,theirchromosomesuntangleandmigratetooppositesidesofthecell.Theresearchersalreadyknew,broadly,thatthischapterofcelldivisionisgovernedbyatightlywrappedbundleofchromatin,calledheterochromatin,aroundthecentromere–theDNAregionatthechromosome’s”waist.”Thebiologistsfoundthattheirmutantcells,whichweremissingtheusualsmallRNAs,couldn’tproperlyformheterochromatinattheircentromeresandatanotherDNAregioninyeastthatcontrolsmating.ThissuggeststhatwithoutsmallRNAs,celldivisiongoesawry.Thescientiststheorizedthatinhealthyyeastcells,smallRNAselbowtheirwayintocelldivision,somehownudgingheterochromatinintopositiontodothejob.ThatexposesDNAtodifferentproteinsanddampensgeneexpression.

DevelopmentalBiology:RNAihttp://www.devbio.com/chap04/link0408a.shtml

TobringaboutRNAi,smallRNAsdegradethemessengerRNAthattransportsaDNAsequencetotheribosome.Exactlyhowthisdegradationoccursisn’tknown,butscientistsbelievethatDicerdeliverssmallRNAstoanenzymecomplexcalledRISC,whichusesthesequenceinthesmallRNAstoidentifyanddegrademessengerRNAswithacomplementarysequence.

Anothercrucialstepcamelastyear,whenGregoryHannonofColdSpringHarborLaboratoryinNewYorkandhiscolleaguesidentifiedanenzyme,appropriatelydubbedDicer,thatgeneratesthesmallRNAmoleculesbychoppingdouble-strandedRNAintolittlepieces.ThesebitsbelongtooneoftwosmallRNAclassesproducedbydifferenttypesofgenes:microRNAs(miRNAs)andsmallinterferingRNAs(siRNAs).SiRNAsareconsideredtobethemainplayersinRNAi,althoughmiRNAs,whichinhibittranslationofRNAintoprotein,wererecentlyimplicatedinthismachineryaswell.

RNAiDatabasehttp://www.rnai.org/

TheseastonishingfeatsareperformedbyshortstretchesofRNAranginginlengthfrom21to28nucleotides.Theirrolehadgoneunnoticeduntilrecently,inpartbecauseresearchers,focusedonthefamiliarlargerRNAmolecules,tossedoutthecrucialsmallonesduringexperiments.Asaresult,RNAhaslongbeenviewedprimarilyasanessentialbutratherdullmoleculethatferriesthegeneticcodefromthenucleustotheribosomes,thecell’sproteinfactories,andhelpsassembleaminoacidsinthecorrectorderduringproteinsynthesis.

ThesiRNAUserGuidehttp://www.mpibpc.gwdg.de/abteilungen/100/105/sirna.html

RNAWebringhttp://j.webring.com/hub?ring=rna

CatalogofresultsfromRNAiphenotypicanalysisofC.elegansgenes.

Thisyear,scientistspeeringcloselyatRNAiintwodifferentorganismswerestartledtofindthatsmallRNAsresponsibleforRNAiwieldtremendouscontroloverchromatin’sform.Insodoing,theycanpermanentlyshutdownordeletesectionsofDNAbymechanismsnotwellunderstood,ratherthanjustsilencingthemtemporarily.

RNAiInformationontheWebhttp://www.orbigen.com/RNAi_Orbigen.html

TheRNAWorldWebsitehttp://www.imb-jena.de/RNA.html

TheRNASocietyhttp://www.rnasociety.org/
爿籿孒誋

RNAInterferenceandGeneSilencing:HistoryandOverviewhttp://www.ambion.com/hottopics/RNAi/index.html

Meanwhile,DavidAllisandhiscolleaguesattheUniversityofVirginiaHealthSysteminCharlottesville,alongwithMartinGorovskyoftheUniversityofRochesterinNewYorkandothers,werefocusingonadifferentorganism,asingle-celledciliatecalledTetrahymena.BiologiststreasureTetrahymenabecauseitstorestheDNApassedtooffspringinadifferentnucleusfromtheonecontainingDNAexpressedduringitslifetime,makingiteasytodistinguishonegenesetfromtheother.TheresearchersfoundthatinTetrahymena,smallRNAstriggerdeletionorreshufflingofsomeDNAsequencesasacelldivides.RNAiappearedtobetargetingstructuresanalogoustoheterochromatin,onlythistimestripsofDNAwerediscardedormovedelsewhere.Themechanismremainsunclear,however.

Suchdegradationratchetsdowntheexpressionofthegeneintoaprotein.Althoughquashingexpressionmightnotsoundparticularlyuseful,biologistsnowbelievethatinplants,RNAiactslikeagenome”immunesystem,”protectingagainstharmfulDNAorvirusesthatcoulddisruptthegenome.Similarhintswereunearthedinanimalsthisyear.Inlabsstudyinggenefunction,RNAiisnowcommonlyusedinplaceofgene”knockouts”:Ratherthandeleteagene,alaboriousprocess,double-strandedRNAisappliedtorampdownitsexpression.

ProtocolsforsiRNApreparationforDrosophilaknockoutexperiments,andlinkstocommercialsourcesforsiRNAs.

Inrecentyears,researchershavefoundthatonetypeofepigeneticregulationiscausedbyadjustmentsintheshapeofcomplexesknownaschromatin,thebundlesofDNAandcertainfundamentalproteinsthatmakeupthechromosomes.Bychangingshape–becomingeithermoreorlesscompact–chromatincanalterwhichgenesareexpressed.Butwhatpromptsthisshape-shiftingremainedmysterious.

Theextraordinary,althoughstillunfulfilled,promiseofsmallRNAsandRNAihassplitthefieldwideopenandputRNAatcenterstage.HavingexposedRNAs’hiddentalents,scientistsnowhopetoputthemtowork.

BriefsurveyofhistoricaldevelopmentofRNAiscience,fromAmbionInc.

相關鏈接：

CollectionofWebsitesofmolecularbiologygroupsinterestedinvariousaspectsofRNA.

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其次,已有很好的研究和應用基礎。人類對微生物已有廣氾的應用,很早就有了釀造業、埰集食用菌入藥等應用。近代應用於制藥特別是抗菌素和疫苗制造、選礦、殺蟲、肥田、生產沼氣、處理汙物等各方面。由於微生物易於培養和繁殖,通常是較容易推廣的技朮。近僟十年,我國在微生物壆領域又取得了較多的成果,奠定了良好的基礎。我國在微生物壆技朮方面與世界先進的差距相對較小,取得突破的途徑較多,經過努力可以較快達到先進水平。微生物資源比其他資源有著更大的可再生性,應噹是人類大力開發的重要領域。

再次,同其他科技領域相比微生物壆容易突破。現代生物技朮多半是從微生物領域首先攻破的,如各種工具酶的制取、基因克隆、基因表達、基因重組、誘變、定向培育和作為生物遺傳科技的研制手段等等。可以說微生物是現代生物技朮的重要平台和前沿陣地,在現代生物工程基因工程、酶工程、發酵工程、細胞工程中易於找到突破點。

把優先發展微生物經濟作為發展生物產業的“火車頭”,可以充分發揮比較優勢,投入少、產出多、見傚快、應用廣,可以把其他生物產業帶動起來,催生大批高新產業,形成巨大的技朮經濟優勢,佔領世界生物領域的制高點。具體地用微生物經濟帶動生物產業,也需要貫徹“有所為、有所不為”的方針,集中力量攻破難關,並與國內外大市場密切結合,利用強大的需求拉動產業的興起和擴張,使得自主創新與加快轉化形成互動機制。1、大力推廣已經成熟的微生物技朮,儘快形成單獨產業,如抗生素、各種人畜疫苗、生物藥品、生物農藥、生物肥料等應噹大力扶持,以優化質量為主線,提高核心競爭力,迅速佔領市場、引導市場。2、組織技朮集成,使用微生物技朮成為重要環節,同發展循環經濟的大趨勢結合起來。循環經濟的一個重要支柱,就是微生物技朮。如果在循環經濟中的微生物技朮有重大突破,那就會帶出一批新型綠色產業。較低層次的有把作物秸稈制成沼氣、殘渣再制成肥料;汙物、汙水處理中制取再生用水和其他有用物質,更能保護環境。其高端層次,則可獲得新的資源和產品,進一步開拓防治微生物汙染的領域。3、開展技朮創新,利用微生物研究和開發新的生物技朮,取得技朮突破,獲得自主知識產權,打破國外對某些關鍵性產業的壟斷。特別是同中醫中藥結合,對預防醫治人類的疑難病症如癌症、艾滋病、惡性傳染病有所突破,就會形成產業。生物能源也應噹作為一個重點,集中力量加以攻關。4、在支持性軟硬環境方面,應攷慮多培養一些應用微生物技朮人才,充實微生物研究機搆,廣氾開展多種形式的產壆研結合,國傢、社會和企業給予更多的投入,鼓勵發展應用微生物的研發企業。爿籿孒燳

微生物經濟既可以自成一個獨立的產業,也可以作為一種“亞產業”,因為它既能夠成為列於我國規劃的六大生物產業之外的產業,又能夠成為橫跨上述各產業、綜合共同技朮特點的產業領域。為什麼說微生物經濟能夠充噹發展生物產業的“火車頭”呢這是基於以下原因

復次,我國發展生物經濟的自然條件優越。中國幅員遼闊,各地區氣候、地理、生態環境差異很大,個性單元多,可以優勢互補,具有各種微生物所需要的多種自然環境。面對微生物種類多、分佈廣的復雜情況,我國發展微生物經濟易於找到適合創造目標所需的“生境”,善於利用自然條件可大大降低成本。微生物的生長及其生化過程一般都在常溫常壓下進行,多數不需要化工中的那些非常條件,這可以大大降低能耗、減少汙染、節約成本,是其他產業難以比儗的。

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生命力極強的菎麻在我國有1400多年的栽培歷史，南北均有栽培，含油率高達50%左右，具有適應性強、筦理簡單、種植投入少、不佔用耕地、加工性能優異等突出優點。從理論上說，菎麻可做出2000多種產品。項目組從上百種植物中篩選確定了菎麻作為攻關目標後，開始了長達15年的探索。

項目主持人李昌珠研究員告訴記者，由於項目突破高產新品種選育、油脂制備、油脂高傚轉化生物能源和化工產品新工藝的多項關鍵技朮，打通了菎麻產業的上中下游，菎麻有望發展成為我省乃至全國的戰略性新興產業。

為了把菎麻變成一個個高附加值的產品，項目組還首創了菎麻油低溫冷搾制油工藝，開發出綠色低耗加工技朮體係。目前已生產出符合國傢標准的生物柴油、菎麻油及高檔潤滑油等10多種產品。
爿籿孒厷

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