Click here to load reader
Upload
mandel
View
209
Download
5
Embed Size (px)
DESCRIPTION
第六章 基因表达的调控 本章,我们讨论 4 个问题: 1. 什么是基因表达的调控? 2. 原核生物基因表达调控是如何进行的? 3. 真核生物基因表达调控是如何进行的? 4. 基因表达调控与医学研究. 概 述 一、基因( gene) ( 一 ) 概念 从化学上来说指的是一段 DNA 或 RNA (病毒)顺序,该顺序可以产生或影响某种表型,可以由于突变生成等位基因变异体。 从遗传学上来说代表一个遗传单位、 1 个功能单位, 1 个交换单位和 1 个突变单位。 - PowerPoint PPT Presentation
Citation preview
41.2.3.4.
gene)() DNARNA 111 RNA7P27
1. PhenotypegenetypeLeu+Leu-Leu+Leu- 2.allele 1222DNA
3. 4. 5. 6.
structural gene mRNArRNAtRNADNA
genome 11112111 3
1. RNA polRNARNADNARNA 2. proteintRNAmRNA 1110
DNAprotein
()prokaryote DNAprotein1 eukaryote2
11
1.2.RNA pol DNA pol DNA compt 1.2. 3.
100Britten-Davidsen RNA pol
1 2
1house keeping geneconstitute expression 2indutioninducible genes
60JacobMonodE.coli adaptive enzymeLac operon1 1 11111 1.operon 1mRNACAP
2. P-O
1(inciduble operon)(induction)(inducer)2(repressible operon)(repression)(corepressor)
DNADNA H1H2H1H21.h2h12.h2h1rh1h1H13.h2-rh1 DNA4.105111
DNA h2-rh1H2-H1995bp IRLIRR 995bppalindiomeinvertedrepeat sequenceDNA14bp hin hin995bp995bpPh2h2h2-rh1H2-h1h1995bpPh2h2h2-rh1h1 h1h2
RNA pol: 1. 2.DNAmRNA 3. mRNA
1.2.
1.promoter2.sigma DNADNADNARNA pol RNA pol2,
E.coli40~60bp321 +1O2 RNA pol -10bpATTATAboxpribnow3 -35RNApol1PRPDNA2RNA polP2E.coli42~50 32KD 32 32rpohhipR
-10-3570
4DNAmRNA5Pheat shock responseE.coil. 32,
3. negative-actingproreinrepressor1OPOPODNARNA polOmRNARNA pol P2,effector 4. positive prateactivator21CAP* 2ntrc* ntrc
21inducer2corepressorO*1CAP-catabolic gene activator protein*2Ntrc-Ecolinitrogen metabolismntrB
5.inversion proteinsite-speciFic recombinotion enzymeDNA6.RNA pol-stringent respsnse RNA polRNA polRNArRNA,tRNA tRNAATPpppGpp(-5)ppGpp-4-RNA pol ppGpp-RNA pol RNA pol rRNAtRNA RNA pol rRNAtRNA
7.teminator 33212 127-20bp216~24bp1G,C 1GC226~8ATbp 8.rho() 6 1 2 NTPaseNTPRNA pol
DNARNA pol RNA9.attenuator
RNA polRNARNARNADNADNARNA pol GCRNA polread through
1. 1 -2~3500010005~10% + 2 6019961975
2Lactose operon Lac operon
CAPCAP1122
G- GGLac operonGLac operonG G G cAmp GcAmpcAmpCAPCAPCAPRNA polP CAPCAMP-CAPGG
Arac-CParc PBAD-IO1O2-B-LisomeraseA-LkinaseD-L4opimeraseI-
2 1 Ara operonCAPAracAra15EcoliAra3Ara5 2Ara operon
3 aracaraBAD AraC2CindCrep AraAraCind+AraaraBAD araC AraAraCrep araBADaraC Ara operon Lac operonGcAmp-CAP araCaraBAD Ara operonCindCAMP-CAPCrep Ara
AraAraCreparaO2IDNAaraBAD AraAra+AraCcAMP-CAPCAParaBADaracaraCCindO1C araBADCindBAD
1.3
(1) RNA poloperonDNA1mRNA(2)1operon DNAPmRNAPRNA(3)2 RNA pol1operon1operon2operon
1
2.2+1 2 1 2 33 attenutor,A1 AmRNA31 RNA polRNA pol Trp operon
(trp operoon)1.Trp operon
2.1TrpO2Trp operon TrpTrp Trpfecdback inhibition TrpROR12.5KD42044OTrp4O Ptrp-10-35-10TrpORNA pol
3ATrp operon Trp operon1/70Lac operon1/1000Trp operonLac operonTrp aL
aLE30~60bp4GC8UTrp3,42UGGTrp6700bp
aL 2UGG 4122.33.4GC1.2>2.3>3.4 348U comptaLRNA polaL+90aL TrpTrp-tRNA121.2,2.33.4RNA pol
TrpTrp-tRNA12Trp2334RNAEDCBA aL TrpmRNAEDCBATrp Trp122
compt, SD 1.SDSD Sequence,SDs mRNAAuG3~10bp1RbSSD 1SDsAGGAGG 2mRNAAuG4~13bpAuG4~13bp 3A16SRNAUmRNA 411AuGSDSDs
2.SD 1SDsAuG IL-2PlacSDsAuG 7IL-28IL-2500 2SDs Plac31:0.5:0.2 SDs tRNA
3.mRNASD SDsmRNA :1omrc 23srRNA((erythromycin methylase))23srRNA2057-2060GAAGA,1amrcTrp operon
2mRNA
mRNA1.2,2.3,3.4,4.3SD1SD2
423srRNA1234SD223srRNA1.22.33.4SD223srRNA
23srRNASD2
mRNA 1.3mRNA mRNAmRNAmRNAmRNA 2.mRNA mRNA 1mRNA 2mRNAmRNARNase3RNasemRNA RNasemRNA 3mRNA2~3minNTPmRNAmRNA
mRNApr.pr 1. 11pr.mRNA pr.rRNAprEcolipr553421 250pr.pr. 3pr.mRNApr. 41operonmRNA2pr1
2.RF21 3UAGUGAUAA 1tRNApr.pr. 3 RF1 UAAUAG RF2 UAAUGA RF3 RFRF2 1eIF
2RF2mRNA reading-framemRNA31Pr.311AuGAuG CCA AAA uuu cccAuG/GCA/AAA/UUU/CCCA/UGG/CAA/AAU/UUC/CC open reading-frameDNARNA 3 Pr.11 Pr mRNA53NC
mRNA 5 AUGGGG UAU CUU UGAC UAC GAC 3 NH2 Gly Tyr Leu Asp --Tyr -- Asp---COOH 25 315(AA) RF2340Pr.125AAAUG315AA+11 RF221UU26AAASP2RF2UGA25AA 15RF2mRNA 1523 24 25 26 27 28
RF2 RF2A25UGARF2 RF2 RF2mRNA25AA UGA RF21U 25AA UAG UAG1RF1RF2 25
RNA1.RNAE.coliPr.Pr.
1omPR Pr. omPF omPC2OmPR Pr. Ompc ompc mRNA ompc Pr. micF3micFompF mRNAL44SDsAUGompF mRNA42Pr.ompF.ompc5RNAmRNAmRNAmRNAmRNARNA,micRNAmRNA-interfering complementary RNA
2.RNATn101Tn10terr112Tn10
3 Tn10pinRNAPout23540bp2RNA 2RNA RNA-inRNA-outRNA-outRNA-in8Tn10 TnTnTn10RNA
DNA
DNA1. Rbc 2.gene amplification
chanrRNArDNA40002000000/500rRNAPr.
3.gene rearrangement 1 Pr.IgB Ig22DNA1064.gene modificationDNA DNA/DNA/
/121DNA DNA25CGPr3DNADNaseI
5. 1 166168bpDNA2Pr.Pr.+RNA8000~10000chromosomechromatin DNA1~15% 2Pr. Pr.histone5510H42AAPr.DNA8H1
Pr.Pr.NSerArgPrDNA3Pr.non-histon 300~600high mobility group,HMGH1H5DNA
RNA pol TATAboxconsonsus sequence25~30bpT82A97T93A85AorT100A83AorT83Pr.P
RNA pol-1 12 PDNARNA pol DNA 2 2 ,RNA pol 3I181285.8rRNAsrRNA mRNAPr.-DNATF DTATA+TATA2TFRNA polDNARNA pol P
1.TFDTATAboxPr.-DNA2.RNA polTF D-DNA3.RNA pol 3
1.trans-acting factor DNAPr.Pr. DNA8~15DNA12.3 13 DNAPr. 2 3++RNA pol+cis-acting elementDNA
3.1DNADNA-binding domain 1)zine finger motif DNA2His2cys4cys1Zn TFA9DNA5srRNA45bpRNA pol
2transcriptional activation domainDNA80~100AA13 -acidic -helix domainGlnglutamine-tich donainproproline-rich domain
--helix-loop-helix,HLH100~200AA2-1AA2AADNA-CTF/NF-1DNA-AALeucine zipper
RNA pol2PDNA RNA pol IITATATFIID+TATA RNA pol II TATA+TATAboxPr.-DNApol II pol IIPr.-DNA pol II RNA pol
1.
12 //cAMP-Pr./ Pr.SerThrSP1DNA
DNAPr.Vitelinegen,Pr.Pr.DNARNA polPr.DNAPr.2Pr.-PrPr.-Pr.C-myc Pr. Leu max Pr.
2.Pr. 1Pr. 23. RNA poltrans-acting1looping DNARNA pol 2twisting DNAPr.DNA DNA 3sliding DN4Oozing 14. combinatorial regulation TATATATA box RNA polPr.-DNA open complex
RNAmRNAtRNAtRNAposttranscription processing5 1.mRNA caping5 GpppmNPtailing AA50~200bp 1mRNA 2CBP 2mRNA 2.rRNA 3.tRNA L
mRNA 1.splicing)-mRNArRNAtRNAinterveningsequence
1Option exonexon skipping12Option intron 13Mutually exclusiveexon 21mRNA14Internal splice site
2.1Bax BaxBax/Bcl2 BaxPr.mRNA Bax 6192192AA Bax 5 218 Baz 134562151AA
2IBr NF- B B NF- BI BrNF B/I Br105KD I BrmRNA178672CPr.I Br1I Br2 21AI Br I BrNF- B
mRNAmRNA 1.3H-udR20%mRNA RNA1 2.9nm>9nm15nm 20nmgold sphereRNAtRNA5sRNA frogoocyte mRNA 3.RNA20%RNA 2Pr.RNA
GTP.MET-tRNA40S.MET-tRNAi.GTP 40S.MET-tRNAiGTPmRNA 80s.METtRNA.GTPmRNA 1.Pr. mRNAPr. Pr. mRNA5, Pr.ferritinmRNA530iron-response element 1 1regulatoryiron-binding pro 1Pr.mRNA 2
2. eIF2Pr. eIF2 eIF2() Rbc 3.5-AuG5 3 mRNA
1Pr.90%mRNA1AUGPr.25AUGAUGCAMP-CAMP-Pr.5-AUG(1)1-AUG
4.mRNA5 1517~80 21AUG540S121AUGFN5267mRNA mRNA1.1 mRNA3mRNA 2 mRNA10 ,-Pr.mRNA>10h2. 1mRNA 3AUmRNA 2Pr.mRNA3polyADNADNA1h12 mRNA
3.DNA 1mRNA3mRNA 2Pr.mRNA3Pr.3mRNA 3-Pr.mRNA3mRNA 3mRNA 4 -Pr.mRNA3Pr.mRNA3DNARNAlin-4Lin-14Pr. Lin-42RNA1221340Lin-4RNALin14mRNA3UTRmRNA
1 Pr. 1.fosmyc 2. 3. 1 2N-1AAMet.serThrAlavalcysGlyproAA12AAAAdestabilizing amino acid AAN-MetMet-tRNAN1AA N1AA/1AA
Pr.Pr. signal peptide Pr.Pr.
Pr1.1PrN5~10AAPr.H3N-Met---Leu-Leu-Leu-Val-Gly-Ile-Leu-Phe-Trp-Ala---ER21C4AAPr.ER Lys-Asp-Glu-Leu-Coo-
2.mitochondrion AAAA3~5AA1AAH3N-Met-Leu-Ser-Leu-Arg(+)---3.5AAPro-Pro-Lys-Lys-Lys-Arg-Lys-Val-4. 1FAERSrc Pr.NGlyras Pr.C4cys2src Pr.ras Pr.