瀹為獙瀹ゆ柊闂?/h4>
PNAS锛氫綍宸?璐炬鑺宠棰樼粍鎶ラ亾RNA淇グm6A鍘荤敳鍩洪叾FTO瀵瑰绉峈NA淇グ搴曠墿鐨勫幓鐢插熀鍒嗗瓙鏈虹悊
杩戞棩锛屽寳浜ぇ瀛﹀寲瀛﹂櫌鐨勪綍宸?/span>/璐炬鑺宠棰樼粍鍦?/span>Proceedings of the National Academy of Sciences of the United States of America锛?/span>PNAS锛夊湪绾垮彂琛ㄤ簡棰樹负 鈥?/span>Structural insights into FTO鈥檚 catalytic mechanism for the demethylation of multiple RNA substrates鈥?/span>鐨勭爺绌惰鏂囥�?/span>
FTO瀵逛汉浣撳彂鑲茶嚦鍏抽噸瑕侊紝FTO閰舵椿鍔熻兘鐨勭磰涔变細褰卞搷鍙戣偛鍜屽绉嶇柧鐥呯殑鍙戠敓锛?/span>鍖呮嫭鑲ヨ儢鍜?/span>鐧岀棁绛?/span>銆?/span>N6-鐢插熀鑵哄槍鍛わ紙m6A锛変綔涓?/span>mRNA涓婂惈閲忔渶涓轰赴瀵岀殑鐢插熀鍖栦慨楗帮紝鏄?/span>棣栦釜琚?/span>鎶ラ亾鐨?/span>FTO鍘荤敳鍩?/span>閰舵椿鐢熺悊搴曠墿銆備箣鍚庨檰缁姤閬?/span>FTO鐢熺悊搴曠墿杩?/span>鍖呮嫭mRNA涓?/span>5鈥?/span>甯?/span>绔悗鐨?/span>N6锛?/span>2'-O-浜岀敳鍩哄寲鑵哄槍鍛わ紙cap m6Am锛?/span>锛?/span>snRNA鐨?/span>m6A鍜?/span>m6Am锛?/span>tRNA鐨?/span>N1-鐢插熀鑵哄槍鍛わ紙m1A锛?/span>锛?/span>闄ゆ涔嬪杩樻湁浣撳娲绘�у簳鐗╁崟閾?/span>DNA涓婄殑N6-鐢插熀鑴辨哀鑵哄槍鍛わ紙6mA锛夊拰N3-鐢插熀鑳歌吅鍢у暥锛?/span>3mT锛変笌鍗曢摼RNA涓婄殑N3-鐢插熀灏垮槯鍟讹紙m3U锛?/span>銆?/span>FTO濡備綍璇嗗埆浼楀鐨勬牳閰镐慨楗扮⒈鍩猴紝鏄惁鏈夊偓鍖栭�夋嫨鎬э紝濡備綍缁撳悎澶氱RNA锛?/span>FTO涓轰粈涔堝cap m6Am鐨勬椿鎬ч珮浜庡崟閾?/span>RNA涓婄殑m6A锛屽強FTO涓轰粈涔堝鍗曢摼RNA鎴?/span>DNA涓婄殑m1A娌℃湁娲绘�у嵈瀵?/span>tRNA鎴栬寧鐜粨鏋勪笂鐨?/span>m1A鏈夋椿鎬э紵鍥炵瓟杩欎簺FTO鐨勯叾鍌寲鍒嗗瓙鏈哄埗鏈夊緟浜庤泲鐧?/span>-鏍搁吀澶嶅悎鐗╂櫠浣撶粨鏋勭殑瑙ｆ瀽銆?/span>鐒惰�?/span>FTO铔嬬櫧涓庢牳閰稿簳鐗╃粨鍚堝姏澶急锛岃嚧浣胯幏寰?/span>FTO铔嬬櫧-鏍搁吀澶嶅悎鐗╂櫠浣撶粨鏋勪竴鐩存槸璇ラ鍩熺殑鎸戞垬鍜岄毦鐐广�?/span>
鍖椾含澶у鍖栧瀛﹂櫌浣曞窛/璐炬鑺宠棰樼粍宸у鍦板FTO铔嬬櫧杩涜姘ㄥ熀閰镐綅鐐圭獊鍙樻湁鏁堝湴鎻愬崌浜?/span>FTO涓庢牳閰哥殑缁撳悎鍔?/span>锛?/span>鍚屾椂涓嶇牬鍧?/span>FTO鐨勫簳鐗╁彛琚嬪拰閰舵椿锛岄娆℃垚鍔熻幏寰椾簡FTO-鏍搁吀澶嶅悎鐗╂櫠浣撶粨鏋?/span>锛堝浘1锛?/span>銆傞�氳繃瀵?/span>FTO涓?/span>6mA淇グ鐨?/span>ssDNA澶嶅悎鐗?/span>缁撴瀯瑙ｆ瀽锛?/span>3mT銆?/span>m6A銆?/span>m6Am鍜?/span>m1A鏍歌嫹鍒嗗埆鍙犲悎鍒?/span>FTO-6mA澶嶅悎鐗?/span>缁撴瀯姣斿鍒嗘瀽鍙婁綋鍐呭鐢熷寲瀹為獙锛?/span>寰楀嚭濡備笅缁撹锛?/span>1锛夌浉姣?/span>3mT鎴?/span>m1A绛夊叾浠栫敳鍩哄寲纰卞熀锛?/span>FTO鏇村亸鐖?/span>N6-鐢插熀鑵哄槍鍛ょ⒈鍩?/span>銆?/span>FTO娲绘�у彛琚嬩腑鐨勬皑鍩洪吀R96鍜?/span>E234鐗瑰紓鎬т笌N6-鐢插熀鑵哄槍鍛ょ⒈鍩虹殑鍢屽懁鐜舰鎴愭阿閿浉浜掍綔鐢紝鍚屾椂澶氫釜姘ㄥ熀閰哥粍鎴愪竴涓ǔ瀹氱殑鐤忔按鑵旂敤浜庡浐瀹?/span>N6-鐢插熀鏈濆悜鍙嶅簲涓績銆?/span>2锛?/span>m6A鍜?/span>m6Am鎷ユ湁鐩稿悓鐨?/span>N6-鐢插熀鑵哄槍鍛ょ⒈鍩猴紝鍖哄埆浠呭湪浜庣硸鐜殑2鈥?/span>浣嶇殑鐢插熀銆傞�氳繃缁撴瀯鍒嗘瀽鍜屼綋澶栫敓鍖栧疄楠屽彂鐜?/span>FTO瀵圭浉鍚岀⒈鍩哄簭鍒楃殑RNA涓殑m6A鍜?/span>m6Am鍏锋湁鐩稿悓鐨勫幓鐢插熀娲绘�э紝琛ㄦ槑FTO鐨勫幓鐢插熀娲绘�т富瑕佷緷璧栦簬娲绘�у彛琚嬩腑涓?/span>N6-鐢插熀鑵哄槍鍛ょ⒈鍩虹殑璇嗗埆锛屽井寮辩殑绯栫幆2鈥?/span>浣嶇殑缁撴瀯宸紓骞朵笉浼氶�犳垚FTO瀵?/span>m6A鍜?/span>m6Am鐨勬椿鎬у樊寮傘�?/span>3锛?/span>閫氳繃缁撴瀯鍒嗘瀽鍜屼綋澶栫敓鍖栧疄楠屽彂鐜颁笉鍚岀殑RNA纰卞熀搴忓垪鍜?/span>RNA涓夌淮缁撴瀯浼氬奖鍝?/span>FTO鐨勫幓鐢插熀娲绘�э紝FTO鏇村亸鍚戝ぇ鐨勮寧鐜粨鏋勩�傝繖甯姪瑙ｉ噴浜嗕负浠�涔?/span>FTO瀵?/span>cap m6Am鐨勬椿鎬ч珮浜庡崟閾?/span>RNA涓婄殑m6A锛屽強涓轰粈涔?/span>FTO瀵瑰崟閾?/span>RNA鎴?/span>DNA涓婄殑m1A娌℃湁娲绘�у嵈瀵?/span>tRNA鎴栬寧鐜粨鏋勪笂鐨?/span>m1A鏈夋椿鎬с�?/span>璇ョ爺绌跺伐浣?/span>闃愭槑FTO瀵逛笉鍚?/span>RNA搴曠墿鐨勫偓鍖栨満鐞嗭紝涓?/span>娣卞叆鐮旂┒FTO鐢熺悊鍔熻兘鍙?/span>寮�鍙?/span>FTO灏忓垎瀛?/span>鎶戝埗鍓傦紡婵�娲诲墏濂犲畾浜?/span>鍩虹銆?/span>
鍥?/span>1 FTO-6mA鏍搁吀澶嶅悎鐗╂櫠浣撶粨鏋勫強鍘荤敳鍩?/span>閰舵椿鍒嗗瓙鏈哄埗
涓婅堪宸ヤ綔涓昏鐢?/span>鍖椾含澶у鍖栧闄?/span>浣曞窛/璐炬鑺宠棰樼粍鐨勫崥澹爺绌剁敓寮犵瑧銆侀瓘杩炵幆銆佽倴闆?/span>鍜屼笂娴蜂氦閫氬ぇ瀛?/span>鍖诲闄?/span>寮犺壇璇鹃缁勭殑纭曞＋鐮旂┒鐢?/span>鐜嬮洦蹇?/span>绛夊悎浣滃畬鎴?/span>锛屽悓鏃跺緱鍒颁簡鍖椾含澶у鍖诲閮?/span>鑽闄?/span>姹ゆ柊鏅?/span>璇鹃缁勭殑甯姪銆?/span>璐炬鑺冲拰寮犺壇涓?/span>鍏卞悓閫氳浣滆�咃紝璇ョ爺绌?/span>寰楀埌浜嗗浗瀹剁鎶�閮ㄥ拰鍥藉鑷劧绉戝鍩洪噾濮旂瓑缁忚垂璧勫姪銆?/span>