Noncanonical MicroRNAs and Endogenous siRNAs in Lytic Infection of Murine Gammaherpesvirus 英文参考文献.docVIP

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Noncanonical MicroRNAs and Endogenous siRNAs in Lytic Infection of Murine Gammaherpesvirus 英文参考文献.doc

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Noncanonical MicroRNAs and Endogenous siRNAs in Lytic Infection of Murine Gammaherpesvirus 英文参考文献

NoncanonicalMicroRNAsandEndogenoussiRNAsin LyticInfectionofMurineGammaherpesvirus JingXia1,WeixiongZhang1,2* 1Department of Computer Science and Engineering, Washington University, St. Louis, Missouri, United States of America, 2Department of Genetics, Washington UniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica Abstract MicroRNA(miRNA)andendogenoussmallinterferingRNA(endo-siRNA)aretwoessentialclassesofsmallnoncodingRNAs (sncRNAs) in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNAbiogenesispathway.InordertoidentifynoncanonicalmiRNAsandendo-siRNAsrespondingtovirusinfectionand studytheirpotentialfunction,wesequencedsmall-RNAspeciesfromcellslyticallyinfectedwithmurinegammaherpesvirus 68 (MHV68). In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonicalmiRNAs,includingmiRNAsderivedfromtransferRNAs,smallnucleolarRNAsandintrons, inthehost were identified.ThesenoncanonicalmiRNAsexhibitedfeaturesdistinctfromthatofcanonicalmiRNAsinlengthsofhairpins,base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murineendo-siRNAsdetectedbythesequencingprofiling,anovellocusinthemousegenomewasidentifiedtoproduce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs).Unexpectedly,theSINE-derivedendo-siRNAswerefoundinavarietyofsequencingdataandvirus-infectedcells. Moreover,amurinemiRNAwasup-regulatedmorethan35foldininfectedthaninmock-treatedcells.Theputativetargets oftheviralandtheup-regulatedmurinemiRNAswerepotentiallyinvolvedinprocessesofgenetranscriptionandprotein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune systemduringlyticinfection.OurresultsextendedthenumberofnoncanonicalmiRNAsinmammalsandshednewlighton theirpotentialfunctionsoflyticinfectionof