6 bước điều hòa biểu hiện gen ở tế bào eukaryotes
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6 bc iu ha biu hin gen t bo Eukaryotes
_Phin m_Ct b intron,ni exon (splicing)_mARN gn vi mt s protein c hiu xuyn qua l nhn ra bo tng
_Hy cc mARN khng c dung dch m_Dch m,tng hp protein_S trng thnh ca protein
Sau y l phn trnh by chi tit v 6 bc k trn ca c ch biu hin gen1.Phin m (Transcription)
_nh ngha : Phin m l qu trnh chuyn thong tin di truyn t ADN sang mARN.ADN khng lm khun trc tip tng hp ra protein m thong qua trung gian lmARN.
c im:_Ch c 1 trong 2 mch phn t AND c dung lm khun tng hp ARN theonguyn tc b sung A=U, T=A, GC, CG . mARN cha thng tin ca 1 gen
_ARN-polymerase bm vo ADN lm tch mch v di chuyn theo hng 3 5 trnmch khun ADN, ARN c tng hp theo hng 5 3.
_Cc giai on
+ Khi ng (quan trng nht)+ Ko di+ Kt thc
_S phin m c thc hin theo tng n v phin m:+ Promoter: ni gn ARN-polymerase+ Vng mang m:l trnh t m ha,cha c intron v exon.+ Terminator :vng khng m ha,kt thc s phin m
_C s tham gia ca 3 loi ARN-polymerase:+ ARN-polymerase I: tham gia vo qu trnh phin m rARN 18S, 5,8S ,28S+ ARN-polymerase II chu trch nhim tng hp mARN+ ARN-polymerase III: gip phin m tARN v rARN 5S
Din bin qu trnh phin ma) Giai on khi ng
Cc nhn t tham gia khi ng:_TF II D: nhn bit & gn vo v tr khi ng promoter_TF II A: gn vo TF II D_ARN-polymerase gn vo phc hp TF II A TF II D nh TF II B_TF II F gn ARN-polymerase vo promoter v tr TATA box_TF II E cho php khi ng s phin m_TF II H: s dng helicase tch ADN v 1 ATP oc s dng tch 2mch n
b)Giai o n k o d i
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mARN c tng hp t mch khun theo hng 5 3 nh nhn tTF II S.c)Giai o n k t th cmARN tch khi mch khun. V tr tch ny c nhn bit bi 2
trnh t c bit+ chui nu AAUAAA+ chui nu giu GU hoac giu U
d) Gn chp v thm ui poly A_ Khi mch mARN di 20-30 ribonu . u 5 ni thm cht 7-methylguanylate. Chp ny gip n nh mARN ,bo v chng li s phnhy v gip ribxm nhn bit mAR_ Khi mch mARN tch khi AND ,polyA
polymerase (PAP) ct tanARN ni vi cc nhn t,ng thi gn them vo u 3 chng 200-250A Sau cc qu trnh trn ca phin m to ra c tin mARN,tc mARN
cha trng thnh
N.
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_ Khi mch mARN tch khi AND ,polyA polymerase (PAP) ct tanARN ni vi cc nhn t,ng thi gn them vo u 3 chng 200-250A Sau cc qu trnh trn ca phin m to ra c tin mARN,tc mARN
cha trng thnh.
2. Splicing
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_ Khi mch mARN tch khi AND ,polyA polymerase (PAP) ct tanARN ni vi cc nhn t,ng thi gn them vo u 3 chng 200-250A Sau cc qu trnh trn ca phin m to ra c tin mARN,tc mARN
cha trng thnh.2. Splicing Ct ri cc intron v ni cc exon li vi nhau nh spliceosome (gmsnRNP v cc protein) Hai Nu u tin GU u 5 v AG u 3 ca mi intron l v trnhn bit ct intron ra khi phn t tin mARN C 3 bc c bn :
_ Ct ti bin gii exon-intron ti u 5
+U1 ,U2 bm vo u 5 ca intron ,tip xc vi A+U4,U5,U6 n gn vo to thnh splicesome, ct u 5
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_ ribonu 5G u intron va b ct lin kt vi 2OH ca A nmgn v tr ct 3khang 20-50 ribonu to hnh thng lng
_ Ct ti bin gii exon-intron ti u 3, intron b loi ra v 2exon c ni vi nhau Cui qu trnh ny to thnh mARN trng thnh
rARN t ct b cc an intron m khng cn spliceosome
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3. mARN xuyn qua l nhn ra bo tng
(passage through the nuclear membrane)
mARN gn vi 1 s protein c hiu hnRNP ,nhn din l nhn nh cc th th bntrong mng nhn, xuyn mng nhn ra ngai bo tng theo hng 5- 3
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3. mARN xuyn qua l nhn ra bo tng
(passage through the nuclear membrane)
mARN gn vi 1 s protein c hiu hnRNP ,nhn din l nhn nh cc th th bntrong mng nhn, xuyn mng nhn ra ngai bo tng theo hng 5- 3
4.Hy mARN (nu mARN khng c dchm)(Destruction of the transcript)
Nu mARN khng c dch m,tc khng c qu trnh tng hp protein,th di tc dng ca ribonuclease ,s phn hy phn t mARN ny
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5.Dch m ,tng hp protein (protein synthesis)_ Dch m l qu trnh gii m thng tin di truyn t mARN to thnhprotein tng ng_Ngai mARN ,th 2 nhn t quan trng khc tham gia qu trnh dch m lribxm v ARN vn chuyn
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5.Dch m ,tng hp protein (protein synthesis)_ Dch m l qu trnh gii m thng tin di truyn t mARN to thnhprotein tng ng_Ngai mARN ,th 2 nhn t quan trng khc tham gia qu trnh dch m lribxm v ARN vn chuyn
_ Ribxm c 2 n v di l n v di ln 60S v n v di b 40S
_ Trn 2 n v di :ln v b u c 3 v tr k hiu l A, P v EA (Aminoacyl) l ni tARN mang acid amin nP (Peptidyl) l ni hnh thnh lin kt peptidE (exit) l ni tARN ri khi ribxm
_ARN vn chuyn
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+ u 3 c b 3 CCA+ u DHU cha dihydrouridine+ u 5 c phosphorine ha+u TpsiC cha b 3 T-Psi-C+anticodon cha b 3 i m,c
hiu cho acid amin n mang.
Din bin chnh gm hat ha acid amin v dch m ti ribxm
Hat ha acid amin v gn n vo tARN
_Qu trnh hat ha din ra t bo cht.
_Mi acid amin(aa) s kt hpng ha tr vi tARN c hiu nh nnglng ca ATP, c xc tc bi aminoacyl-tARN. Mi enzyme c hiucho 1 aa v nhng tARN ng vi aa
Aa + ATP aaAMP +PP(pyrophosphate) y l bc hat
ha aa nh ATP to ra amynoacyl-AMP,lin kt gia chng llien kt anhydric acid,mt loai lin kt giu nng lng,khithy phn s to nng lng cho phn ng th 2
Aa-AMP + tARN aa-tARN + AMPBc ny hnh thnh
aminoacyl-tARN. tARN s ginh quyn lien kt vi aa bnggc OH u 3 ca n. y l lien kt cao nng lng,chnhnng lng ny cung cp cho qu trnh to lien kt peptide sau
ny. Cn u NH2 t do ca aa s kt hp vi gc COOHca aa khc to lien kt peptide
Dich m ti Ribxmgm 3 giai an: khi u ,ko di v kt thc1) GIAI ON KHI U( I NI TIATIO N)
_y l giai on m u cho gii m, l giai on hnh thnh Rb honchnh v gn tARN m u vo u 5 ca mARN. N cn cc yu t mu IF (Initiation Factors) tham gia.
_Ribosome s tch nhau ra nh s lin kt ca IF1 v IF3 vi n v dinh, chun b cho gii m.
_IF2-GTP s nht ly aa-tARN ifMet, lin kt n vi n v di nh ti vtr P . vd nh ca Rb n mARN ti m n u 5, sau trt trn 1
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on mARN khun m ha n codon m u_n v di ln ca Rb n lp rp vi n v di nh, giai on khi uhon tt.GTP thy gii to GDP v P, to nng lng tch cc nhn t m ukhi phc hp trn.Tt c c n 11 yu t tham gia: eIF1-A, eIF1-B, eIF2,
eIF2-B, eIF4-A, eIF4-B...
AI ON KO DI (ELONGATION)1. Cc aa-tARN s c nhn t EF-Tu nht ly nh c s hin din caGTP.2. EF-Tu-aa-tARN s n Rb (ang cha tARN m u (Met-tARNMet)hay peptidyl-tARN) ti v tr A ca Rb.3. Qu trnh c sa(proof-reading): Qu trnh ny khng din ra theokiu c acid amin.
4.Khi tm c tARN thch hp, lin kt peptid c hnh thnh gia 2 aa
nh enzim peptidyl transferase. Kt qu: gii phng tARN v tr P khi aa;aa-tARN A by gi tr thnh mt peptidyl-tARN mi.
5. Sau , tARN u tin s chuyn qua v tr E v ri khi Rb, peptidyl-tARN mi chuyn t A sang P. C 2 qu trnh u c s tham gia ca EF-G-GTP, s ct t 1 lin kt P ca GTP. mARN di chuyn tin ti mt codonmi S chuyn di (Translocation)
6. Peptidyl-tARN nh v ti v tr P,codon mi trn mARN s tip tc c ni kt vimt aa-tARN thch hp mi ti v tr A. EF-Ts s phc hi EF- Tu-GTP
7. Cc bc trn s din ra tip tc cho n khi gp m kt thc. Ti sdin ra giai on kt thc (termination)
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GIAI ON KT THC (TERMINATION)
_Khi Rb gp b ba kt thc UAA UAG UGA ti v tr A th cc nhn t RFcng GTPs n v tr A v lin kt vi codon kt thc, trong RF1 nhn bit UAG UAA,RF2 nhn bit UAA UGA
_RF3 l 1 GTPase,khi thy gii s lm t lin kt ca chui polypeptid v peptidyl-tARN, phng thch chui polypeptid. Hai vd ca Rb tch ri nhau ra, bt u mtqu trnh gii m mi.
6.S trng thnh ca phn t protein (Post-translational modification)
_Protein sau khi c tng hp s c gnthem mt s chc ha hc nh acetat,
photphat , lp cu ni disulfide hoc ct b 1an peptid gia protein.
_Tiu biu,mt s protein c phosphorylha nh hnh bn
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_C s to lien kt disulfua gia 2 cystein,sau protein t xon v cun khc li.
_Glucoprotein c to thnh bng cch gnthem glucid vo mch bn ca asparagin,serin, threonin ca protein.
_a s cc protein c fMet l acid amin u tin ca chui peptid, sau khi
protein tng hp xong ,c s ct nhm formyl ca fMet
_Insulin b ct 2 ln sau khi cu ni disulfua c hnh thnh, 1 s peptid ra khi giachui. Kt qu l protein gm 2 chui polypeptide c ni li vi nhau bng cu nidisulfua.
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