A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome.
A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome.
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DOI：
10.1038/emboj.2010.14
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发表时间：
2010-03-17
期刊：
影响因子：
11.4
通讯作者：
Chrzanowska-Lightowlers, Zofia M.
中科院分区：
文献类型：
--
作者：
Richter, Ricarda;Rorbach, Joanna;Pajak, Aleksandra;Smith, Paul M.;Wessels, Hans J.;Huynen, Martijn A.;Smeitink, Jan A.;Lightowlers, Robert N.;Chrzanowska-Lightowlers, Zofia M.
生物信息学分析将未成熟结肠癌转录-1 （ICT1）编码的人类蛋白分类为四个假定的线粒体翻译释放因子家族之一。然而，这还没有得到任何实验证据的支持。由于该家族只有一个成员mtRF1a才能终止所有13种线粒体编码多肽的合成，因此ICT1的真正生理功能尚不清楚。在这里，我们报道了ICT1是一种必需的线粒体蛋白，但与其他可基质溶解的家族成员不同，ICT1已成为人类线粒体体的一个组成部分。释放因子试验表明，尽管ICT1保留了核糖体依赖性PTH活性，但这是不依赖密码子的；这与ⅰ类释放因子中两个促进密码子识别的结构域的缺失一致。核糖体依赖性PTHs常见的GGQ结构域突变导致体外活性丧失，更重要的是，体内细胞活力丧失。我们认为，ICT1可能对停止的线粒体中过早终止的肽基trna部分的水解至关重要。
Bioinformatic analysis classifies the human protein encoded by immature colon carcinoma transcript-1 (ICT1) as one of a family of four putative mitochondrial translation release factors. However, this has not been supported by any experimental evidence. As only a single member of this family, mtRF1a, is required to terminate the synthesis of all 13 mitochondrially encoded polypeptides, the true physiological function of ICT1 was unclear. Here, we report that ICT1 is an essential mitochondrial protein, but unlike the other family members that are matrix-soluble, ICT1 has become an integral component of the human mitoribosome. Release-factor assays show that although ICT1 has retained its ribosome-dependent PTH activity, this is codon-independent; consistent with its loss of both domains that promote codon recognition in class-I release factors. Mutation of the GGQ domain common to ribosome-dependent PTHs causes a loss of activity in vitro and, crucially, a loss of cell viability, in vivo. We suggest that ICT1 may be essential for hydrolysis of prematurely terminated peptidyl-tRNA moieties in stalled mitoribosomes.
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影响因子：
16
作者：
Soleimanpour-Lichaei HR;Kühl I;Gaisne M;Passos JF;Wydro M;Rorbach J;Temperley R;Bonnefoy N;Tate W;Lightowlers R;Chrzanowska-Lightowlers Z
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Chrzanowska-Lightowlers Z
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