Nat Commun. 2018 一种以环状形式的LINC-PINT编码的肽抑制胶质母细胞瘤中的致癌转录伸长.pdfVIP免费

ARTICLEApeptideencodedbycircularformofLINC-PINTsuppressesoncogenictranscriptionalelongationinglioblastomaMaoleiZhang1,2,KunZhao1,2,XiaopingXu1,2,YibingYang1,2,ShengYan1,2,3,PingWei4,HuiLiu5,JianboXu6,FeizheXiao7,HuangkaiZhou1,2,8,XuesongYang1,2,NunuHuang1,2,JingleiLiu1,2,KejunHe1,2,KepingXie9,GongZhang10,SuyunHuang11,12&NuZhang1,2CircularRNAs(circRNAs)arealargeclassoftranscriptsinthemammaliangenome.AlthoughthetranslationofcircRNAswasreported,additionalcodingcircRNAsandthefunctionsoftheirtranslatedproductsremainelusive.Here,wedemonstratethatanendo-genouscircRNAgeneratedfromalongnoncodingRNAencodesregulatorypeptides.Throughribosomenascent-chaincomplex-boundRNAsequencing(RNC-seq),wediscoverseveralpeptidespotentiallyencodedbycircRNAs.Weidentifyan87-amino-acidpeptideencodedbythecircularformofthelongintergenicnon-protein-codingRNAp53-inducedtranscript(LINC-PINT)thatsuppressesglioblastomacellproliferationinvitroandinvivo.Thispeptidedirectlyinteractswithpolymeraseassociatedfactorcomplex(PAF1c)andinhibitsthetranscriptionalelongationofmultipleoncogenes.TheexpressionofthispeptideanditscorrespondingcircRNAaredecreasedinglioblastomacomparedwiththelevelsinnormaltissues.OurresultsestablishtheexistenceofpeptidesencodedbycircRNAsanddemon-stratetheirpotentialfunctionsinglioblastomatumorigenesis.DOI:10.1038/s41467-018-06862-2OPEN1DepartmentofNeurosurgery,FirstAffiliatedHospitalofSunYat-senUniversity,Guangzhou510080GuangdongProvince,PRChina.2GuangdongProvincialKeyLaboratoryofBrainFunctionandDisease,Guangzhou510080Guangdong,PRChina.3DepartmentofNeurosurgery,FirstAffiliatedHospitalofGuangxiMedicalUniversity,Nanning530000GuangxiProvince,PRChina.4DepartmentofPathology,FudanUniversityShanghaiCancerCenter,FudanUniversity,Shanghai200433,PRChina.5DepartmentofSpineSurgery,FirstAffiliatedHospitalofSunYat-senUniversity,Guangzhou510080Guangdong,PRChina.6DepartmentofGastroenterologySurgery,FirstAffiliatedHospitalofSunYat-senUniversity,Guangzhou510080Guangdong,PRChina.7DepartmentofScientificResea...