RNAi-mediated DNA silencing
http://www.100md.com
《细胞学杂志》
Moazed/AAAS
After embracing RNAi's ability to silence and degrade transcripts, biologists have eyed reports that RNAi is required for heterochromatin assembly with skepticism. With new results showing that siRNAs are essential for targeting a heterochromatin-associated protein complex to DNA, André Verdel, Danesh Moazed (Harvard Medical School, Boston, Massachusetts), Shiv Grewal (National Cancer Institute, Bethesda, Maryland), and colleagues think that skepticism is now unfounded. "It leaves no doubt that RNAi is very directly involved in heterochromatin formation," says Moazed.
Previous work showed that deletion of factors required for RNAi disrupted heterochromatin formation in yeast, implying that RNAi was involved in transcriptional gene silencing. Now, the authors have purified an RNAi effector complex (RITS) that contains Ago1 (the homologue of the siRNA-associated protein Argonaute), a heterochromatin associated protein Chp1, a novel protein Tas3, and small siRNAs complementary to centromeric DNA repeats.
Mutations of Tas3 disrupt heterochromatin formation and block association of methylated histone-3 with DNA, a phenotype that resembles the previously described mutants of Ago1 and Chp1. Targeting the RITS complex to DNA requires siRNAs—in yeast strains lacking Dicer, the enzyme that produces siRNAs, the proteins associate but fail to find chromatin. RITS may recruit histone modifying enzymes to chromatin and initiate heterochromatin assembly. Although Verdel et al. expect these associations to be transient, they are working to detect them directly.
Reference:
Verdel, A., et al. 2004. Science. 10.1126/science.1093686(siRNAs target RITS to heterochromatin.)
濠电儑绲藉ú鐘诲礈濠靛洤顕遍柛娑卞枤椤╃兘鏌涘☉鍗炲閺夆晜妫冮弻娑樷枎韫囨挴鍋撴禒瀣劦妞ゆ巻鍋撻柛鐘崇〒濡叉劕鈹戦崶鈹炬灃閻庡箍鍎卞Λ娑㈠焵椤掑鐏︽鐐差儔楠炲洭顢旈崨顓炵哎濠电偠鎻徊鎯洪幋鐘典笉闁挎繂鎷嬮崵鍫澪旈敂绛嬪劌闁哥偞鎸抽弻鏇㈠幢閺囩姴濡介柣銏╁灠缂嶅﹪骞婇敓鐘茬疀妞ゆ挾鍋熸禒鎰版⒑閸︻厐鐟懊洪妶鍥潟闁冲搫鎳庤繚闂佺ǹ鏈粙鎺楁倵椤斿墽纾奸柡鍐ㄥ€稿暩婵犫拃鍕垫疁鐎殿喖鐖煎畷姗€濡歌閸撴垶绻涚€涙ḿ鐭婂Δ鐘叉憸閺侇噣顢曢敂钘夘€涘┑锛勫仜婢х晫绮欐繝鍥ㄧ厸濠㈣泛锕ら弳鏇熸叏閻熼偊妯€闁轰礁绉撮悾婵嬪礃椤垳鎴烽梻浣筋嚃閸犳捇宕濊箛娑辨晣缂備焦岣块埢鏃堟煟閹寸儑渚涢柛鏂垮暣閺岋繝宕掑顓犵厬缂備焦顨呴ˇ閬嶅焵椤掑喚娼愮紒顔肩箻閿濈偤鏁冮崒姘卞摋闁荤娀缂氬▍锝囩矓閸喓鈧帒顫濋鐘闂侀潧娲ゅú銊╁焵椤掑偆鏀版繛澶嬬洴瀹曘垽濡堕崶銊ヮ伕閻熸粎澧楃敮妤咃綖婢舵劖鍋ｉ柛銉娑撹尙绱掓潏銊х畼闁归濞€閹粓鎸婃径澶岀梾濠电偛顕慨楣冨春閺嶎厼鍨傞柕濞炬櫆閸嬨劌霉閿濆懎鏆熸俊顖氱墦濮婃椽顢曢敐鍡欐闂佺粯鎼换婵嬬嵁鐎ｎ喖绠ｆ繝濠傚閹枫劑姊洪幐搴ｂ槈闁哄牜鍓熷畷鐟扳堪閸曨収娴勫銈嗗笂閻掞箓寮抽鍫熺厱闁瑰搫绉村畵鍡涙煃瑜滈崜姘潩閵娾晜鍋傞柨鐔哄Т鐟欙箓骞栭幖顓炵仯缂佲偓婢跺⊕褰掑礂閸忚偐娈ら梺缁樼箖閻╊垰鐣烽敓鐘茬闁肩⒈鍓氶鎴︽⒑鐠団€虫灁闁告柨楠搁埢鎾诲箣閻愭潙顎撳┑鐘诧工閸燁垶骞嗛崒姣綊鎮╅幓鎺濆妷濠电姭鍋撻柟娈垮枤绾鹃箖鏌熺€电ǹ啸鐟滅増鐓￠弻娑㈠箳閺傚簱鏋呭┑鐐叉噹闁帮絾淇婇幘顔芥櫢闁跨噦鎷�After embracing RNAi's ability to silence and degrade transcripts, biologists have eyed reports that RNAi is required for heterochromatin assembly with skepticism. With new results showing that siRNAs are essential for targeting a heterochromatin-associated protein complex to DNA, André Verdel, Danesh Moazed (Harvard Medical School, Boston, Massachusetts), Shiv Grewal (National Cancer Institute, Bethesda, Maryland), and colleagues think that skepticism is now unfounded. "It leaves no doubt that RNAi is very directly involved in heterochromatin formation," says Moazed.
Previous work showed that deletion of factors required for RNAi disrupted heterochromatin formation in yeast, implying that RNAi was involved in transcriptional gene silencing. Now, the authors have purified an RNAi effector complex (RITS) that contains Ago1 (the homologue of the siRNA-associated protein Argonaute), a heterochromatin associated protein Chp1, a novel protein Tas3, and small siRNAs complementary to centromeric DNA repeats.
Mutations of Tas3 disrupt heterochromatin formation and block association of methylated histone-3 with DNA, a phenotype that resembles the previously described mutants of Ago1 and Chp1. Targeting the RITS complex to DNA requires siRNAs—in yeast strains lacking Dicer, the enzyme that produces siRNAs, the proteins associate but fail to find chromatin. RITS may recruit histone modifying enzymes to chromatin and initiate heterochromatin assembly. Although Verdel et al. expect these associations to be transient, they are working to detect them directly.
Reference:
Verdel, A., et al. 2004. Science. 10.1126/science.1093686(siRNAs target RITS to heterochromatin.)