Self Containment, a Property of Modular RNA Structures, Distinguishes microRNAs 英文参考文献.docVIP

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Self Containment, a Property of Modular RNA Structures, Distinguishes microRNAs 英文参考文献.doc

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Self Containment, a Property of Modular RNA Structures, Distinguishes microRNAs 英文参考文献

SelfContainment,aPropertyofModularRNAStructures, DistinguishesmicroRNAs MilerT.Lee1,JunhyongKim2,3* 1GenomicsandComputationalBiologyProgram,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica,2Departmentof Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania,UnitedStatesofAmerica Abstract RNAmoleculeswilltendtoadoptafoldedconformationthroughthepairingofbasesonasinglestrand;theresultingso- calledsecondarystructureiscriticaltothefunctionofmanytypesofRNA.Thesecondarystructureofaparticularsubstring of functional RNA may depend on its surrounding sequence. Yet, some RNAs such as microRNAs retain their specific structures during biogenesis, which involves extraction of the substructure from a larger structural context, while other functional RNAs may be composed of a fusion of independent substructures. Such observations raise the question of whetherparticularfunctionalRNAsubstructuresmaybeselectedforinvarianceofsecondarystructuretotheirsurrounding nucleotidecontext.WedefinethepropertyofselfcontainmenttobethetendencyforanRNAsequencetorobustlyadopt thesameoptimalsecondarystructureregardlessofwhetheritexistsinisolationorisasubstringofalongersequenceof arbitrarynucleotidecontent.Wemeasureddegreeofselfcontainmentusingascoringmethodwecalltheself-containment index and found that miRNA stem loops exhibit high self containment, consistent with the requirement for structural invarianceimposedbythemiRNAbiogenesispathway,whilemostotherstructuredRNAsdonot.Furtheranalysisrevealeda trendtowardhigherselfcontainmentamongclusteredandconservedmiRNAs,suggestingthathighselfcontainmentmay beacharacteristicofnovelmiRNAsacquiringnewgenomiccontexts.WefoundthatmiRNAsdisplaysignificantlyenhanced self containment compared to other functional RNAs, but we also found a trend toward natural selection for self containmentinmostfunctionalRN