核糖核酸酶Z(Ribonuclease Z、RNase Z、3′ tRNase,在不同生物中的名称包括ElaC、ZiPD、RNase BN、TRZ1等)是一种参与tRNA生合成的核糖核酸酶,为内切酶,属依赖型金属水解酶,编码此蛋白的基因于2002年被发现[1][2]

核糖核酸酶Z
枯草杆菌的核糖核酸酶Z与tRNA结合的结构图
识别码
EC编号 3.1.26.11
CAS号 98148-84-6
数据库
IntEnz IntEnz浏览
BRENDA英语BRENDA BRENDA入口
ExPASy英语ExPASy NiceZyme浏览
KEGG KEGG入口
MetaCyc英语MetaCyc 代谢路径
PRIAM英语PRIAM_enzyme-specific_profiles 概述
PDB RCSB PDB PDBj PDBe PDBsum

tRNA基因转录产生tRNA前驱物(pre-tRNA)后,其5′端会被核糖核酸酶P切割,3′端则被核糖核酸酶Z切割,随后再由CCA tRNA核苷酸转移酶英语CCA tRNA nucleotidyltransferase在其3′端加上CCA三个碱基,以生成成熟的tRNA[1][3][4]。核糖核酸酶Z切割位点下游位点的CC会抑制其切割活性,因此已被加上CCA的成熟tRNA不会再被其切割[2][注 1],此外tRNA前驱物5′端序列的长度也可能影响核糖核酸酶Z切割的活性[6][7]

酿酒酵母[8]大肠杆菌[9]枯草杆菌[10]海栖热袍菌[11]等生物的核糖核酸酶Z结构均已被解出[6]

演化与功能

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三域生物皆有核糖核酸酶Z,已被定序的所有真核生物古菌以及许多细菌皆有之,但变形菌门的细菌多不具此酵素。自然界中存在两型的核糖核酸酶Z,较短的RNase ZS长280至360个氨基酸,见于三域生物[2];较长的RNase ZL长度约为前者两倍,在演化上应是由前者经基因重复产生,只见于真核生物[2]。RNase ZS会以二聚体的形式切割tRNA,RNase ZL则是以单体的形式作用,且有研究显示后者的切割活性比前者的高许多[6]

脊椎动物植物以外的真核生物(包括酿酒酵母、粟酒裂殖酵母黑腹果蝇秀丽隐杆线虫模式生物[2])经常只有RNase ZL[12];而同时具有RNase ZL和RNase ZS的生物中两者在细胞中的位置可能不同[2],例如模式植物阿拉伯芥分别有两个RNase ZS与RNase ZL,前者一个位于细胞质,一个位于叶绿体中,后者一个位于细胞核与粒线体,一个仅见于粒线体[13][14];酿酒酵母仅有RNase ZL,位于细胞核与粒线体中[8]

人类的RNase ZL(ELAC2)基因有两个起始密码子,可转录产生两种不同的mRNA,其中较长者包含一粒线体导向序列,会被送入粒线体中,负责切割粒线体基因组编码的tRNA前驱物;较短者则会被送入细胞核中,切割细胞核编码的tRNA前驱物,除产生成熟tRNA外,也参与tRNA片段(tRNA fragment)的生成,进而影响细胞内各种小RNA量的平衡[2][15][16]已知有ELAC2基因的突变前列腺癌心肌病变相关[6][8][17][18]。人类的RNase ZS(ELAC1)则位于细胞质中,其功能仍不甚清楚,有研究指其可能参与解决转译核糖体停滞的反应途径,停滞的核糖体上P位点的tRNA 3′端会被内切酶ANKZF1英语ANKZF1切割,将与其连结的多肽链和末端的CCA碱基一起移除,造成tRNA最末端的核苷酸形成2′,3′-环磷酸(2′,3′-cyclic phosphate),ELAC1可能可切割此结构,使tRNA重新产生有活性的3′端,得以再被CCA tRNA核苷酸转移酶作用接上CCA而重新利用[19][20]

切割其他RNA

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除tRNA前驱物外,核糖核酸酶Z可能还可切割其他与tRNA前驱物结构相似的RNA。核糖核酸酶P与核糖核酸酶Z可切割MALAT1(一个长链非编码RNA)的3′端,产生MALAT1相关胞浆小RNA(mascRNA)[21];另有一3′端和MALAT1高度相似的长链非编码RNAMEN β RNA可能也可被核糖核酸酶P与核糖核酸酶Z切割,产生类似mascRNA的小RNA[22]。阿拉伯芥编码tRNAGly的基因下游紧接著编码snoR43家族的snoRNA基因,两者会共同转录成一RNA前驱物,并被核糖核酸酶Z切割,以产生成熟的tRNA与snoRNA[23]

参见

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  • 核糖核酸酶E英语Ribonuclease E:某些细菌具有的一种核糖核酸酶,亦为内切酶,tRNA前驱物的3′端可被其切割后,再经由其他外切酶切割产生成熟tRNA,为tRNA 3′成熟的另一机制,不依赖核糖核酸酶Z。部分真核生物可能也有类似机制[2]

注脚

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  1. ^ 此机制有许多例外情形,相较于真核生物tRNA末端的CCA皆是转录后才加上,许多细菌的tRNA基因末端即编码CCA,意即tRNA前驱物中具有CCA,但仍可被核糖核酸酶Z以较低的活性切割。海栖热袍菌的核糖核酸酶Z可能不受CCA抑制,可正常切割含有CCA的tRNA前驱物[2][5]

参考文献

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