Retroviral RNA Dimerization and Packaging The What, How, When, Where, and Why 英文参考文献.docVIP

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Retroviral RNA Dimerization and Packaging The What, How, When, Where, and Why 英文参考文献.doc

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Retroviral RNA Dimerization and Packaging The What, How, When, Where, and Why 英文参考文献

Pearls RetroviralRNADimerizationandPackaging:TheWhat, How,When,Where,andWhy SilasF.Johnson,AliceTelesnitsky* DepartmentofMicrobiologyandImmunology,UniversityofMichiganMedicalSchool,AnnArbor,Michigan,UnitedStatesofAmerica TheEncapsidatedViralGenome:WhatIs Packaged? on some of these hairpins contain palindromes, allowing one gRNAtobasepairvia‘‘kissing’’interactionswithasecondgRNA (Figure 1B). This initial dimer contact is followed by structural transitions that extend intermolecular basepairing to form the encapsidateddimerlinkage[1]. Retroviral genomic RNAs (gRNAs) are packaged as dimers, joined near their 59 ends in non-covalent linkages that withstand modest heat treatment but dissociate at ,65uC. Determinants of gRNAdimerizationandrecruitmentforpackagingmaptothesame ,100to,300baseregionsandare,forthemostpart,physically and genetically inseparable [1]. SyntheticRNAs containing these sequencesdimerizeinvitro.Becausetransplantingthesesequences ontoacellmRNAconfersselectivepackaging,andablatingthem greatlyreducesgRNApackaging,thesesequencesareknownasY (psi),for‘‘packagingsignal’’(Figure1A)[2]. Despite 25 years of research and impressive advances in understandingsecondarystructure,westilllackathree-dimensional understanding of any virus’s Y/DLS and what, minimally, is necessaryforpackaging.Conflictingreportsmayreflectcomplica- tionsinteasingapartelementsinamultifunctionalgenomeregion. ThepropensityofretrovirusestopackagesuboptimalRNAsinthe absenceofgRNAs,differencesamongretroviruses,andtheabsence ofuniformnamingconventionsalsocloudthepicture. Within virions, gRNAs are coated with a basic viral protein callednucleocapsid(NC)atadensityofaboutoneNCperfiveto eight RNA bases [3]. This nucleoprotein complex resides within thematurevirioncore.TotalgRNAlength,wereitinanA-helix, exceedsthecoreinnerdiameterbymorethan30-fold[4].Thus, encapsidatedgRNAishighlycondensed.Theco-packagedgRNAs likelyarenotalignedalongtheirlengthsbecausetheyareidentical andcannotbasepairinregister,but