Five Questions about Viruses and MicroRNAs 英文参考文献.docVIP

Pearls FiveQuestionsaboutVirusesandMicroRNAs BryanR.Cullen* DepartmentofMolecularGeneticsMicrobiologyandCenterforVirology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica MicroRNAs(miRNAs)are,22-ntregulatoryRNAsexpressed by all multicellular eukaryotes [1]. Humans encode .700 miRNAs and similar numbers are likely to exist in other mammalian species. Almost all cellular miRNAs are initially transcribed by RNA polymerase II (Pol II) as part of a long, capped,polyadenylated primarymiRNA(pri-miRNA)precursor. The miRNA forms part of one arm of an RNA stem-loop that consists of an ,32-bp imperfect stem flanked by unstructured RNA sequences. This stem-loop is recognized by the nuclear RNaseIIIenzymeDrosha,whichcleavesthestemtoliberatean ,60-ntpre-miRNAhairpin.Thepre-miRNAisthentransported to the cytoplasm where it is cleaved by a second RNase III enzyme,calledDicer,whichremovestheterminallooptogenerate the miRNA duplex intermediate. One strand of this duplex is incorporated into the RNA-induced silencing complex (RISC), where it acts as a guide RNA to direct RISC to complementary mRNA species [1]. Depending on the level of complementarity, RISC can either cleave bound mRNAs and/or inhibit their translation.InhibitionofmRNAtranslationgenerallyrequiresfull complementarity of the mRNA to nucleotides 2 through 7 or 8 fromthemiRNA59end—themiRNAseedregion.Theprimary, andpossiblysole,functionofmammalianmiRNAsisthereforeto actasspecificpost-transcriptionalinhibitorsofmRNAfunction. WhatDoViralmiRNAsDo? Only a small numberofmRNA targets ofviral miRNAshave beendefined,soacompleteanswertothisquestioniscurrentlynot possible. However, the emerging picture [4] suggests that viral miRNAsmayservetwomajorfunctions.Ontheonehand,several viralmiRNAshavebeenshowntoinhibittheexpressionofcellular factors that play a role in cellular innate or adaptive antiviral immuneresponses. Examplesoftheinhibitionofhostcellfactors involvedinmediatingimmuneresponsesincludethenatural