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Exploration of Small RNAs 英文参考文献
Review
ExplorationofSmallRNAs
Hideya Kawaji, Yoshihide Hayashizaki*
ABSTRACT
(i)smallRNAproduction:aprecursorRNAiscleavedto
produceasmalldouble-strandedRNA(dsRNA),wherethe
precursorcanbeahairpin-structuredRNAoralongdsRNA
inthecaseofmicroRNA(miRNA)orsmallinterferingRNA
(siRNA),respectively;(ii)RNPassembly:theresultingsmall
RNAisloadedintoanRNPcomplex,and(iii)genesilencing:
theRNPsuppressesitstargetgene,wherethetarget
recognitionisguidedbytheloadedsmallRNA,andthe
silencingactivityismediatedbytheproteinscomposingthe
RNPatthepost-transcriptionalortranscriptionallevel[5].
Thismachineryisadoptedinawiderangeoforganisms.
Althoughtheoverallpathwaysresembleeachother,thereare
substantialdifferencesbetweenorganisms(Figure1).In
metazoans,twoRNaseIIIendonucleases,DroshaandDicer,
contributetoaprocessofsmallRNAproduction.Drosha
cleavesalongprimarytranscriptincludingastem-loop
(termedprimarymiRNA,orpri-miRNA)nearthebaseofthe
stemtoreleaseahairpinstructure,termedprecursormiRNA
(pre-miRNA).Dicercleavespre-miRNAoralongdsRNA
(precursorofsiRNA)toproduceasmalldsRNA,onlyone
strandofwhichisloadedintotheRNP[6].Homosapiens,Mus
musculus,andCaenorhabditiseleganshaveonlyoneDicergene,
whichcontributestobothmiRNAandsiRNAproduction.On
theotherhand,thesetworolesareencodedbydistinctgenes
inseveralorganisms.Drosophilamelanogasterhastwoproteins
ofDicer,DCR-1,andDCR-2,whichareusedformiRNAand
siRNA,respectively[7].ArabidopsisthalianahasfourDicer
orthologues,DCL1toDCL4,butnoDrosha.DCL1
F
orseveraldecades,onlyalimitednumberof
noncodingRNAs,suchasribosomalandtransferRNA,
havebeenstudiedinanydepth.Inrecentyears,
additionalspeciesofnoncodingRNAshaveincreasinglybeen
discovered.Ofthese,smallRNAspeciesattractparticular
interestbecauseoftheiressentialrolesinprocessessuchas
RNAsilencingandmodi?cations.Detailedanalysesrevealed
severalpathwaysassociatedwiththefunctionofsmallRNAs.
Althoughthesepathwaysshowevolutionalconservation,
therearesubstantialdifferences.Advancedtechnologiesto
pro?leRNAshaveacceleratedthe?eld
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