B细胞淋巴瘤内miR1792基因转录调控机制研究

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1、ThesisofDefenseforDoctorofPhilosophyTranscriptionalregulationofmiR·17—92●■■I■o■‘express10nInB-ceIIIymphomasDefender：MingJiMentor：HuYi—qiaoProfessorChenJian．xiuKaiFuAssociateProfessor(theU．S．)DepartmentofBiologicalScienceandTechnologySchoolofLifeScience，NanjingUniversityNanji

2、ng．P．R．CHINA-一，March2010In仃oductionIntroductionMicroRNAs(miRNAs)arenon—coding，single—strandRNAs，whichnegativelyregulatetheirtargetgeneexpressionpost—transcriptionally1-4．VariousmiRNAsareover-orunderexpressedindifferenttypesofcancerinhumanandmayfunctionaseithertumorsuppressor

3、soroncogenes5-13．miRNAsareafamilyofsmallendogenous，non-codingRNAs．BiogenesisofmiRNAsdifferf吣motherclassesofsmallRNAs(Figure1)．MicroRNAscanbeprocessedby3’untranslatedregion(UTR)ofmRNAs，introns，longnon．codingRNAs，transposonsandsnoRNAs33，34．Firstly，miRNAsgenearetranscribedasmon

4、o—orpolycistronic，long，primaryprecursortranscripts(pri—miRNAs)．Thepri—miRNAsincludeacupandpoly-Atailprocessedtoshort，about70ntstemp—loopstructuresinthecellnucleus．Thentheyarecleavedintoshortprecursorhairpins．bythenuclearRNase川一likeenzymeDrosha．Subsequently，pre—miRNAhairpinsa

5、reexportedtothecytoplasmbyExportin一5．ThentheyareprocessedbyasecondRNaseII—likeenzyme，termedDicer，into22ntduplexes，followedbytheasymmetricassemblyofoneofthetwostrandsintoafunctionalmiRNPormiRISCbybindingcomplementarysequencesinthe3’UTRofmRNAs，eithermediatetranslationalrepress

6、ionordirectmRNAcleavage35．ThedifferencebetweenmiRNAandtheothertypessmallRNAsisthatthelatterdiversfrommuchlongerhairpinsorfrombimolecularRNAduplexesorfrOmprecursorswithoutanysuspecteddouble—strandedcharacter．ThestudiesongenescontrollingdevelopmentaltiminginC．elegansfoundthatc

7、ellswithmutatedlin-4repeatthecelldivisionpatternandfailtodiiferentiate32．miRNAlet一7controlsthetransitionfromthefourthlarvalstagetotheadultstageandmir-48，mir-241，mir一84controlthedevelopmentaltransitionfromtheL2toL3stage36．Thisresultsinthedevelopmentalretardationindicatethatth

8、emiRNAsplayanimportantroleindevelopmentaltiming．In打oducdon—————————————————