MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains 英文参考文献.docVIP

MicroRNAExpressionandRegulationinHuman, Chimpanzee,andMacaqueBrains HaiYangHu1.,SongGuo1.,JiangXi1,ZhengYan1,NingFu2,XiaoyuZhang3,CorinnaMenzel4 ,Hongyu Liang3,HongyiYang3,MinZhao3,RongZeng2*,WeiChen4,5,SvantePa¨a¨bo6,PhilippKhaitovich1,6* 1KeyLaboratoryofComputationalBiology,CAS–MPGPartnerInstituteforComputationalBiology,ChineseAcademyofSciences,Shanghai,China,2KeyLaboratoryof SystemsBiology,InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai,China,3CollegeofLife Science,NortheastForestryUniversity,Harbin,China,4MaxPlanckInstituteforMolecularGenetics,Berlin,Germany,5MaxDelbru¨ckCenterforMolecularMedicine,Berlin InstituteforMedicalSystemsBiology,Berlin-Buch,Germany,6MaxPlanckInstituteforEvolutionaryAnthropology,Leipzig,Germany Abstract Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an importantroleintheestablishmentofhuman-specificphenotypes.However,themolecularmechanismsunderlyingthese expressionchangesarelargelyunknown.Here,wehaveexploredtheroleofmicroRNA(miRNA)intheregulationofgene expressiondivergenceamongadulthumans,chimpanzees,andrhesusmacaques,intwobrainregions:prefrontalcortex andcerebellum.Usingacombinationofhigh-throughputsequencing,miRNAmicroarrays,andQ-PCR,wehaveshownthat upto11%ofthe325expressedmiRNAdivergedsignificantlybetweenhumansandchimpanzeesandupto31%between humansandmacaques.MeasuringmRNAandproteinexpressioninhumanandchimpanzeebrains,wefoundasignificant inverserelationshipbetweenthemiRNAandthetargetgenesexpressiondivergence,explaining2%–4%ofmRNAand4%– 6%of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA–driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastomacelllines.Finally,w