【doc】肌肉抑制素基因与RNA干扰的应用前景

【doc】肌肉抑制素基因与RNA干扰的应用前景 肌肉抑制素基因与RNA干扰的应用前景 207?7?7??????6???w???????????k?????????) ?????y??:1003]S2843(2005)ZK]S0020]S04 ???????k?]?????NRNA?????????h???? ???V,?????w 3 ,????,??????,?????? (?????6???w???[???????N???9????,?,??610041) ??7???:?c???????????????k?]???????S??????,????RNA???????9??????.???i??RNA???????9?h???????k?]???? ?b?????h????. ???C??:???????k?]????;????;RNA???? ?b???8????:S8137?7?7?7?7?7?7?7????C?4???2:A7?7?7?7? ?k?B???[5 ???3???????V(),??,?????6???w?????????]?????N?W???;?a?h???????S???[ 3, ?????????????h???9???h???????????????w??,?????h?????????a?????????????????w???h. ?h?S???s???????w?????z????????,???????]?,???????0?P??????]n????]M?w?????????[?????k?]???????????[ ????,???????????,?E?S?????????h?w?????z??????????.RNA???????9???????????h,?E?????????????????? ???f???S??????.?8RNA???????9???h???????[?????k?]??????????,?????5????????????????,???????w???? ??????. 17??????[?????k?]?????N???????? 1.17??????[?????k?]???? ?????[?????k?](myostatin,MSTN)???? [1] ,????GDF-8????(growthdifferentiationfactor8),?9TGF-:? (transforminggrowthfactorbeta,???y?[??????:?)???????bGDF???????,??.TGF-:??9???????k???????8?y???8 ?????a??.Myostatin???????5TGF-:????????,??????????,N-???5???H???8???h???????????o,?????a?????? ???????????h????;???E???????y????,?w?h?I?[???z?w?E?u4?f?h????(RSRR)???,????????????????;????C -?e???3?e9?f???????????h?????[???z?w?E.Myostatin????????26KD???,????????,?8???7???y???g?[?8?? ??. 1.27????????? ???h1807????????Culley [2] ?u?h???b??????????????,?d?h?????????????a???5?????7???y???)?5?R??2 ?f??????????,?????d???????????S??????,?X???720?y??60?????????????????w?????????????S??.?????? ???y???????9????72?w??72?)??72???????9?????h???b???????????0?P????,???Z?0???????R??,??????.1983??, ?????h?????????b????????????????,???????????O???????????a??,???????]???N??. 1.37????????k?]?????????? 1997??????JohnHopkins?w????Mcpherron??Lee?h?S???:???????[?????8?y????????????,???????????? ??(double-musclinggene),???????h????PCR???9,???G?h?A?]??????cDNA?????b???e??GDF-8,???7???? ??cDNA???o [3] .?????h???????b???0????,?9?????????[?:??????,???a???:???,???????????????????????[ ???N????,?????????[?????5???????:?????h [4??6] ,?V?8?????R?E?????[?????k?]????]SMyostatin????,?????0 ?y?E?u?a?????????????[?N?????????w.Grobet???a???8???8?????????[?4???8??,??????Myostatin?????????? :200-10-11 :1981-. ,?????w,????,??????,??????:???????k?]?????NRNA?????????h????217?7?7? ?9?]?,??]n????]M?????? [7] . McPherron??Grobet???????K??????:?????????????O???????9?u??Myostatin?????y?2???o???[?????K?] ?,??.McPherron [8] ???a?????????????9?????2?]????Myostatin????,?????R?????P???g???h.?????hMyostatin ???????2?]????,?????????7?????????[?????w,???????????????h???O??????,?????????????????P?2?]?? 261%,?K?S???????A?]?????????????????????[?A?]????86%. Thomas [9] ???8?R?K???????y???w??????Myostatin?????h?????7C2C12?,?????????????????b,?????????? Myostatin???????????????????????????N?,?????????????[?????????,????.???????NMyostatin???,???????? ???5???k???h,??????Myostatin?????k?,????????????,???K?????????[?,?????[?:??. 1.47????????k?]???????K???w?????????0?w ?????a???????????L,Myostatin???o?h?1???????y???Z?b?9??????????.?h?]??MyostatinC-???????E???? ??????????,?w?]72?A?]72??72?f72???G???G???K???w?E100%,????72?????????????51??3?f?????R?K,???NMyo2 statin?????h?1?f??????????????. ???M,McPherron????Myostatin?????h???????????Z???,???f?????????b????.?????????????[,???????? ?????I???????????????????E,???N?h?????????a?R?K???????b????.?X?N??Ji [10] ?????[???????[?f???????? ??????,???????????k?]??mRNA?z???8?:????????,?h?0??????72?672?K72??72??72?A??72??72???????????5?8?:,?X ?e?????6.?K?S?h???????????????b???5???????k?]?8?:.Sharma [11] ????????Myostatin?????h???B???,???f?? ?????b???5????,?z???8?:?h???????A???????????????b.???y,?0???????b???????7?????????H??. 1.57????????k?]???????[???????? ???????k?]???????z?????h?9???????[?????[?:???????????h,?????k?????[??????,?????E?u?y?????u?a ?????????????[???y???w,??????????. ?E??????GDF-8???[????????,McPherron???a???????????????????A?]ES??????GDF-8????,?8???? ?????h???????E?uC???E???u?z??ES?????????R???A?]????,?a???U????????GDF-8?????????(???A?]???? ?,?z???[??,?K?S???f???????[???A?]?w30%????,???????????[???w2??3?R.GDF-8???[???????w?h?????? ?????v????????????,???[?8???h???8???E?k???5?????????S??. ???y,?????????N???????k?]???????????????????????y?????0???????????k???h,Myostatin???????????( ???A?]?N???????????????0?????670%.????,???????????????(???A?]???????????????????9?0?????????6. Shama [11] ?????????N,????????????,?????????????????????????????k?]????????????,???????????k?] ?????h???????????[?8???Z?b?[?????????h.???y,???5???????????k?]?N?,???????????N?d?????????[?5??. 1.67????????k?]???????S?????? ???A?]Myostatin???????????N,?S???3???????????????????????????S??,?X?????a????????Myostatin?? ??????72?????????????S??. Gonzalez-Cadavid [12] ?a???S???8???????????k?]????????????????????2q32,2,????????7.7kb,???3??3 ?f?y?O????2?f???e??,???e??1?????e??2?8?e?E1.8kb??2.4kb.?5?f?y?O???y?2???h?????????8?e?E:125, 124??126.???????h?,???????????b?K?L????,???7???k?????????????h.?,???I?3?b???????k?]???e???N???0 ???????,????. Sonstegard [13] ???8?????f?????[?????k?]????,??????????????15??????????15q2.3.cDNA?5???f?????X (openingreadingframe,ORF)?y?2376?f?h???????P???????o???,,?3?e?5?f?y?O?????-?f???e??.?w?J???[ ?? [14] ???f??Myostatin?????????????????o????.?]??????,???f??Myostatin?????????P????????,?????????? ?P???? ?u?w??72???2 [5] ?????????GMy???????????o,?h?????????GMy??DN???o???E?4??????,?, ???7??????GDF????,???????????????k?4,???????G?????????????b?8????????GDF????,???????S?? . 1 ostatinostatincA -8-8 227?7?7??????6???w???????????k?????????) ???????N????????. 27?RNA???????????? ???I?????????????.?????a?????R?????????????????????????,,?????????????S???????????o???6???? ???????[???????????S???b.?h?]?????????????S???????I?),???????S???????????????????9?R???????????[ ????.RNA????(RNAinterference,RNAi)???9?8?E?????????S???????????????S??. 2.17?RNAi RNAi?9????RNA(dsRNA)?????????0?w????????????????.?d?h?????A??????RNA??????72???0?7?z???[ ????????????????????,???????K??mRNA????,???K???????????????????????E?u??????.RNAi?9?[?????b?? ?????h?????????2?K?????????????:???E?k. 2.27?RNAi?????? ?????????f????????????,?????a??RNAi?????????????????????S??.RNAi??????1998?????????N,???[ ?,???7???h??????72????72?R?????[???????S???b.?h2001?????G???????h?????????????????b?,?????hRNAi ???9???k????????,???i??RNAi???9???h???????[???????S???????? [16] .????,RNAi???9???h???????[?????? ?????????S???b???????,??;?????h?????????????????????????????????S???b?????d?hRNAi???9???7???? ???????????N???????h????????????????????????. RNAi?????h????????????,?S???????d?hRNAi???????????5???7???7???????????-?????h,?E???? [17] 72?? ???? [18] ???????????????????????S??.???y,RNAi?????J????????,?5?d?????]?J??,?l?????]????.?h?????? ???a???S???b,RNAi???9?????????;?7?????R?U?????a???b?R?K???????)?Z?P????. RNAi???E???6???]?????S??????,?E?N?????????????????????8???????????[?????????h????.RNAi???R ???]????????????72??????72???????9?????????Z?W?,,???9???U???z???u??,???????[72????72???????????P?m?? ???????a?S???3??????. 37????????k?]?NRNA?????????h???? ?????????????h?w?????S??,?z?????b?h?r?????????h?).Myostatin?9?h????72???????????????b???????h ?????0?w???k???????R??????????????????,???????????????y?E?u,?u???m??????????????.?u???????????? ?5?r?????a72?[???[????72?r??????72???2??????????,???KMyostatin?9???????h???????????????8????????.?? ??,?a???????G????????????,????Myostatin????,???????????[?[???????h???G,?K?a????Myostatin???????9, ?????GMyostatin???????P????,???k?????????[??,???????????,?c.?S??Myostatin???????????????,?N?????? ?[?????????:???E?8???5???????8???A??,?K???8?E?????a???h???????????????????????S??. Myostatin???????????????]???,??,?E?d?h?????????????????????9????????Myostatin???????????????? ???6?????????????I.?k?K,?????????o???f??,???????????H???%?3??????????????????????,???a?????????? ?????a?[?????????5???w???h???h?????????d?h.?hRNAi???I?S???????h?S???????????w???????K??,?8RNAi ?h?????????k?]???????S?????h?R?%?????????]?????????I?)?????r????????,?E?S?????????????M??,?????? ????????. ?a???8???[?????????d?hRNAi???????????????k?]????,???[?????????????????????????w????????.?K ?S,?d?hRN?????????k?]?????????????6???E?u???K??,?????5???7?????????????w???K?R?????????W???? ?????????????????4,?????????????????S??,?9???????????Z?b???f???????S?????6????,RN?h???]???? ?)?????h?a?1???M???k??,?X???????i?????8?h???]???????[???d?h?b???g???w?????h Ai .Ai . ,?????w,????,??????,??????:???????k?]?????NRNA?????????h????237?7?7? ???:???C: [1]7?BellingeRH,LiberlesDA,IaschiSP,etal.Myostatinanditsimplicationsonanimalbreeding:areview[J].AnimGenet,2005,36(1): 1??6. 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[10]7?JiS,LosinskiRL,CorneliusSG,FrankGR,etal.Myostatinexpressioninporcinetissues:tissuespecificityanddevelopmentaland postnatalregulation[J].AmJPhysiol,1998,275:1265??1273. [11]7?SharmaM,KambadurR,MatthewsKG,etal.Myostatin,atransforminggrowthfactor-betasuperfamilymember,isexpressedin heartmuscleandisupregulatedincardiomyocytesafterinfarct[J].JCellPhysiol,1999,180(1):1??9. [12]7?Gonzalez-CadavidNF,TaylorWE,YarasheskiK,etal.Orgnizationofthehumanmyostatingeneandexpressioninhealthymenand HIV-infectedmenwithmusclewasting[J].ProcNatlAcadSciUSA,1998,95:14938??14943. [13]7?SonstegardTS,RohrerGA,SmithTP,etal.Myostatinmapstoporcinechromosome15bylinkageandphysicalanalyses[J].Anim Genet,1998,29(1):19??22. [14]7??w?J???[,??????,???4??.?f???[?,???k?]?????y?2???o???8??[J].?[?????9,2001,10(6):1??3. [15]7??u?w??,???2,?]???T,??.?G?[???8?y????GDF-8cDNA??????72?????????????y[J].?[?????Z????,2001,17(4):460?? 462. [16]7?CampbellTN,ChoyFY.RNAinterference:past,presentandfuture[J].CurrIssuesMolBiol.2005,7(1):1??6. [17]7?RadhakrishnanSK,LaydenTJ,GartelAL.RNAinterferenceasanewstrategyagainstviralhepatitis[J].Virology.2004,323(2):173 ??181. [18]7?BerkhoutB.RNAinterferenceasanantiviralapproach:targetingHIV-1[J].CurrOpinMolTher,2004,6(2):141??145. ApplicationprospectsofmyostatingeneandRNAinterference SUChang,XUYa2ou,MAWei,YUJian2guo,MAODe2cai (CollegeofLifeScienceandTechnology,SouthwestUniversityforNationalities,Chengdu610041,P.R.C.) Abstract:Inthispaper,advancementofresearchonmyostatingeneandfunctionofRNAinterferenceaerre2 viewed.Inaddition,theprospectofapplicationofRNAinterferencetechniquetomyostatingeneissumma2 rized. Kyy;;RNfewords:mostatingenedouble-muscleAintererence