The Drosophila modigliani (moi) gene encodes a HOAP-interacting protein required for telomere protection
The Drosophila modigliani (moi) gene encodes a HOAP-interacting protein required for telomere protection
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DOI：
10.1073/pnas.0812702106
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发表时间：
2009-02-17
影响因子：
11.1
通讯作者：
Gatti, Maurizio
中科院分区：
文献类型：
--
作者：
Raffa, Grazia D.;Siriaco, Giorgia;Gatti, Maurizio
已经鉴定了几种保护果蝇端粒免受融合事件的蛋白质。它们包括UbcD 1、HP 1、HOAP、Mre 11-Rad 50-Nbs（MRN）复合物的组分、ATM激酶和推定的转录因子Woc。在这些蛋白质中，只有HOAP被证明特异性地定位于端粒。在这里，我们表明，modigliani基因编码的蛋白质（Moi），富集只在端粒，共定位和物理相互作用与HOAP，并需要防止端粒融合。Moi由双顺反子CG 31241基因座编码。该基因座产生一个单一的转录本，其中包含2个指定不同基本功能的ORF。这些ORF之一编码20-kDa Moi蛋白。另一个编码一个60 kDa的蛋白质同源的RNA甲基转移酶，是不需要端粒保护（果蝇Tat样）。Moi和HOAP与保护人类端粒的蛋白质复合物shelterin的组分具有几种特性。HOAP和Moi在进化上并不保守，不像其他参与果蝇端粒保护的蛋白质。类似地，没有一个shelterin亚基在果蝇中是保守的，而大多数人类nonshelterin蛋白质具有果蝇同源物。这表明HOAP-Moi复合物，我们称之为“末端蛋白”，在果蝇端粒的DNA序列独立组装中起着特殊的作用。我们推测这种复合物在功能上类似于shelterin，其以序列依赖的方式结合染色体末端。
Several proteins have been identified that protect Drosophila telomeres from fusion events. They include UbcD1, HP1, HOAP, the components of the Mre11-Rad50-Nbs (MRN) complex, the ATM kinase, and the putative transcription factor Woc. Of these proteins, only HOAP has been shown to localize specifically at telomeres. Here we show that the modigliani gene encodes a protein (Moi) that is enriched only at telomeres, colocalizes and physically interacts with HOAP, and is required to prevent telomeric fusions. Moi is encoded by the bicistronic CG31241 locus. This locus produces a single transcript that contains 2 ORFs that specify different essential functions. One of these ORFs encodes the 20-kDa Moi protein. The other encodes a 60-kDa protein homologous to RNA methyltransferases that is not required for telomere protection ( Drosophila Tat-like). Moi and HOAP share several properties with the components of shelterin, the protein complex that protects human telomeres. HOAP and Moi are not evolutionarily conserved unlike the other proteins implicated in Drosophila telomere protection. Similarly, none of the shelterin subunits is conserved in Drosophila, while most human nonshelterin proteins have Drosophila homologues. This suggests that the HOAP-Moi complex, we name "terminin,'' plays a specific role in the DNA sequence-independent assembly of Drosophila telomeres. We speculate that this complex is functionally analogous to shelterin, which binds chromosome ends in a sequence-dependent manner.