Nuclear Accumulation of an Uncapped RNA Produced by Drosha Cleavage of a Transcript Encoding miR-10b and HOXD4 英文参考文献.docVIP
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Nuclear Accumulation of an Uncapped RNA Produced by Drosha Cleavage of a Transcript Encoding miR-10b and HOXD4 英文参考文献
NuclearAccumulationofanUncappedRNAProducedby
DroshaCleavageofaTranscriptEncodingmiR-10band
HOXD4
SzeLynnCalistaPhua1,V.Sivakamasundari2,YuShao1,XiaohanCai1,Li-FengZhang1,ThomasLufkin2,
MarkFeatherstone1*
1SchoolofBiologicalSciences,NanyangTechnologicalUniversity,Singapore,2GenomeInstituteofSingapore,Singapore
Abstract
Patterningoftheanimalembryo’santero-posterior(AP)axisisdependentonspatiallyandtemporallyregulatedHoxgene
expression. The murine Hoxd4 gene has been proposed to harbour two promoters, an upstream promoter P2, and a
downstream promoter P1, that lie 5.2 and 1.1 kilobase pairs (kb) upstream of the coding region respectively. The
evolutionarilyconservedmicroRNA-10b(miR-10b)geneliesintheHoxd4genomiclocusintheintronseparatingthenon-
coding exons 4 and 5 of the P2 transcript and directly adjacent to the proposed P1 promoter. Hoxd4 transcription is
regulatedbya39neuralenhancerthatharboursaretinoicacidresponseelement(RARE).Here,weshowthattheexpression
profilesofHoxd4andmiR-10btranscriptsduringneuraldifferentiationofmouseembryonalcarcinoma(EC)P19cellsareco-
ordinately regulated, suggesting that both Hoxd4 and miR-10b expression is governed by the neural enhancer. Our
observationthatP1transcriptsareuncapped,togetherwiththemappingoftheir59ends,stronglysuggeststhattheyare
generated by Drosha cleavage of P2 transcripts rather than by transcriptional initiation. This is supported by the
colocalizationofP1andP2transcriptstothesameposteriorexpressiondomaininthemouseembryo.TheseuncappedP1
transcriptsdonotappeartopossessanInternalRibosomalEntrySite(IRES),butaccumulatewithinmultiplepunctatebodies
withinthenucleussuggestingthattheyplayafunctionalrole.Finally,similaruncappedDrosha-cleavedP1-liketranscripts
originatingfromtheparalogousHoxb4/miR-10alocuswerealsoidentified.Weproposethatthesetranscriptsmaybelongto
anovelclassofregulatoryRNAs.
Citation:PhuaSLC,SivakamasundariV,ShaoY,CaiX,ZhangL-F,etal.(2011)NuclearAccumulationofanUncappedRNAProducedbyDroshaCleavageofa
TranscriptE
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