computational approaches to trna-derived small rnas 2017 wei-lin xu-匠人.pdf

该【computational approaches to trna-derived small rnas 2017 wei-lin xu-匠人 】是由【刘备文库】上传分享，文档一共【12】页，该文档可以免费在线阅读，需要了解更多关于【computational approaches to trna-derived small rnas 2017 wei-lin xu-匠人 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。:..non-codingRNAReviewComputationalApproachestotRNA-DerivedSmallRNAsWei-LinXu,YeYang,Yi-DanWang,Liang-HuQu*andLing-LingZheng*KeyLaboratoryofGeneEngineeringoftheMinistryofEducation,StateKeyLaboratoryofBiocontrol,SchoolofLifeSciences,SunYat-senUniversity,Guangzhou510275,China;******@.(W.-.);******@.(.);******@.(Y.-.)*Correspondence:******@.(L.-.);******@.(L.-.)Tel.:+86-020-84112517(L.-.)AcademicEditor::23November2016;Accepted:26December2016;Published:4January2017Abstract:tRNA-derivedsmallRNAs(tDRs)areagroupofsmall,non-codingRNAsderivedfromtransferRNAs(tRNAs).Theycanbeclassi?edastRNAhalvesandtRNA-derivedsmallRNAfragments(tRFs).-generationsequencing(NGS)techniquesallowalargeamountofsmallRNAdeep-,,wesummarizedthetoolsanddatabasesfortDRidenti?cationandcollection,withtheaimofhelpingresearcherschoosethebesttoolsfortheiranalysisandinspiringtheinventionorimprovementoftoolsinthe?:next-generationsequencing;tRNA-derivedsmallRNA;tRNAhalves;tRNA-derivedsmallRNAfragments;identi?cation;-derivedsmallRNAs(tDRs)inalmostallbranchesoflife[1–12].IthasbeensuggestedthatthesetDRsarenotproductsoftherandomdegradationoftransferRNAs(tRNAs),,viralinfectionsandtumordevelopment[13–18].tDRsareclassi?edastRNAhalvesandtRNA-derivedsmallRNAfragments(tRFs).tRNAhalvesaregeneratedbyasinglecleavageattheanticodonofmaturetRNAs,andtheirlengthsrangefrom30ntto35nt[1].ThebiogenesisoftRNAhalvesismostlyinducedbystress,suchasoxidativestress[1].tRFs,however,aregeneratedfrombothprecursor(pre-tRNAs)andmaturetRNAsthroughDicer-dependentor-independentprocesses,,thisclassi?cationoftDRsisnotde?,[19].Recently,prehensivelydetecttDRsinsilico[20].?,inthisreview,wefocusonlyoneukaryotictDRs,-codingRNA2017,3,2;doi::..Non-codingRNA2017,3,,tRNAgenesaretranscribedbyRNApolymeraseIII,andtheresultingproducts(precursortRNAsorpre-tRNAs)undergofurtherprocessingbeforematuration(maturetRNAs).Theseprocessesremovethe5’end(5’leader,byRNaseP)andthe3’end(3’trailer,byRNaseZ)ofpre-tRNAsandthenaddthe5’-CCA-3’(CCA)trinucleotidetothe3’?cationtogeneratenon-canonicalbasesalsooccurwiththeseprocesses[21–23].tDRscanberoughlyclassi?,amemberoftheRNaseT2family,andangiogenin,amemberoftheRNaseAsuperfamily,areresponsibleforthecleavagetoproducetRNAhalvesinyeastandmammaliancells,respectively[13,24,25].Rny1pandangiogeninpossesslittlesubstratespeci?-inducedsituations[26,27].Angiogeninissecretedandendocytosedintothecytoplasm[28].Typically,theseenzymesareinhibited,andstressinducestheirreleasefromtheinhibitors[29].TwogroupsoftRNAhalveshavebeendiscovered,namely5’halvesand3’halves[29].Besides,sexhormone-dependenttRNA-derivedRNAs(SHOT-RNAs)werefoundtobeconstitutivelyexpressedinhumanbreastandprostatecancers[17].TheywereconsideredtRNAhalves,sharecounterpartsof5’and3’halves,,theexpressionofSHOT-RNAsisinducedbysexhormones,andtheyaregeneratedfromtRNAspeciesdifferentfromthoseoftRNAhalves[17].’tRNAhalvesinhibittranslationthroughthedisplacementofelF4G/A(eukaryotictranslationinitiationfactors)fromthemRNAtranscripts[13,30].ThompsonandParkerproposedfourpossiblefunctionalmodelsoftRNAhalves:theinhibitionoftranslationthroughnickedtRNAs,plexwithotherunknownproteins,guidingtheinhibitionoftranslationthroughtheirassociationwithArgonauteorPiwi,andguidingthecleavageofmRNAsviatheirinteractionwiththetRNAprocessingenzymesRNaseZorRNaseP[29].tRFs,however,areproducedfrompre-,fourtypesoftRFshavebeenidenti?edandcharacterizedbytheirprovenanceontRNAs:tRF-1s,tRF-5s,tRF-3s,andi--1sresultfromthecleavageof3’trailerfragmentsofprecursortRNAsbyRNases,includingDicerandRNaseZ[11,19,31],andtheyusuallybeginexactlyafterthe3’-endsofmaturetRNAs(5’-CCA-3’tailsexcluded)andpossesspoly-Usattheir3’-ends[19].tRF-5saregeneratedbycleavageintheD-loopoftRNAsbyDicer,oftentimeswithadenineastheir3’-ends[19,31].tRF-3sresultfromcleavageintheT-loopbyDicer,angiogeninandothermembersoftheRNaseAsuperfamilyandarefragmentsofthe3’endofmaturetRNAs(Aatthe3’end);thecleavageusuallyoccursbetweenA/UandA/Unearthe3’-endofthetRNAs[19,30,31].i-tRFsareenrichedwithintheinternalregionsofmaturetRNAs,andtheyusuallystraddletheanticodonandbeginrightafterthesecondordownstreamnucleotideofthe5’-endsoftRNAs[32].Recently,apreviouslyundescribed5’leader-exontRNAfragmenttypewasdiscoveredtobeassociatedwiththelossofspinalmotorneuronsinCLP1-kinasedeadmice[30,33].Thesefragmentsstraddlethe5’leadersequenceofpre-tRNAsandthe5’[31,34].Ithasalsobeenshownthatthedisplacementofpro-oncogenictranscriptswithtRFsfromtheRNA-ountforthesuppressionofhumanbreastcancerprogressionbythetRFs[18].Inaddition,thetRNA3’externaltranscribedspacersmightbeexcisedandfunctionasaspongetoreducenoiseintranscription[35].Figure1showsthegeneralpathwaysfortDRbiogenesis.:..Non-codingRNA2017,3,-derivedsmallRNAs(tDRs).ells,-derivedsmallRNAfragments(tRF-1s)and5’leader--5s,tRF-3s,i-tRFs,5’halvesand3’,developmentandmetabolismofprimitiveeukaryotes[36,37].Inthemouse,thematurespermenrichmentoftDRswasdiscovered,icfactorsorasregulatorsofendogenousretro-elementspriortoimplantationoftheembryo[10,38,39].Inhumans,tDRshavebeenfoundinseveralhumancancercelllines,buttheircorrelationtotumorigenesisandprogressionremainselusive[16–19,40–42].Comparedwiththoseinanimals,[43,44].AmorerecentstudyrevealedtheexistenceofconservedtDRsinArabidopsisthaliana,itrellapatens[45].?,studiesontDRscouldbeclassi?edintothreecategories:identifyingthetDRs;analyzingtDRfunctions;,andthefollowingisageneralreviewofthetoolsanddatabasesfortDRs.:..Non-codingRNA2017,3,,putationalsolutionstotDRidenti?cationwillbesummarized:generaltoolsnotspeci?ctotDRidenti?cationinearlystudies,mand-linepipelinesdesignedfortDRidenti?cation,andtheintegratedwebservertRF2Cancerwithuser--sequencingdataanalysisisto?,[16,19,37,46,47],bowtie/bowtie2[48,49],exonerate[40],andtheself-madestringmatchingalignmentalgorithmtomapsmallRNAsfromtheNGSdataandidentifytDRsfromthem[50].:thestrategyproposedbyTelonisetal.,-fragmentreadsbymappingthemtothegenome,whereasthetDRmappermapsthetrimmedreadsdirectlytotRNAs[32,50].,,andevenofdifferentanticodonsspecifyingthesameaminoacids,,thethreenucleotidesimmediatelydownstreamofthe3’endsoftRNAsarereplacedApriortomapping,A-trinucleotide-,theypermittedmultiplehitsongenomictRNAsandretainedthereadsspanningexon–,theyidenti?edafourthclassoftRFs,i-tRFs,andencouragedscepticismtotherationalityofmappingthereadstothetRNAspacealoneintRFidenti?,thisstudydidnotprovideoff-the-shelfsoftware[32].Almostatthesametime,SelitskyandSethupathyreleasedtDRmapper,acommand-oolfortheidenti?cation,namingandquanti?cationoftDRs[50].OfparticularnoteisthattDRmapperadoptedan“errortype”hierarchicalalignmentschemetohandlepossiblemismatchesattributedtochemicalmodi?,-tRNAsortRNAswithsomede?nedrequirements,suchasexactmatcheswithmatureorpre-tRNAs,,annotatedandquanti?,?cally,readsmappabletobothtRNAsandotherregionsinthegenomearepossiblyindicativeofnewunannotatedtRNAlocibutarenotreadsderivedfromgenomictemplatesotherthantRNAs[50].Incontrast,,duetotRNAlookalikesofnuclearandmitochondrialtRNAsandpartialtRNAsequences,thereadsmappablebothtotRNAsandotherknownnon-,themappingtotRNAsalonewouldgeneratehigherfalsepositivesandexaggeratetheexpressionofcertaintRFsfromgiventRNAs[32,50].Thus,allthesecontroversiescanbereducedtothebalancebetweenobtainingfalsepositiveandfalsenegativeresults[51].tDRmapperaimedatidentifyingmorepotentialtRFsatthecostofincreasedfalsepositives,,werecentlydesignedtRF2Cancer,anintegratedwebserverforidentifyingtRFsfromsmallRNAsequencingdataandevaluatingtheirexpressionincancers[48].tRF2CancerconsistsoftRF?nder(tRFidenti?cationfromsmallRNAdeep-sequencingreads),tRFinCancer(inspectexpressionoftRFsacrosscancertypes)andtRFBrowser(originsandchemicalmodi?cationsoftRFs).Priortomapping,tRF?ndermaps:..Non-codingRNA2017,3,25of12theprocessedreadstothehumangenomeandhumantranscriptsequencestoremoveexogenousreadsandreadsotherthantRFs(suchasmRNAs,miRNAs,snoRNAs,snRNAs,rRNAsandrepeats).Thisstephelpstoreducethefalsepositiveresultsderivedfromnon-?nderthenmapsthereadstotR