Mouse apolipoprotein B editing complex 3 (APOBEC3) is expressed in germ cells and interacts with dead-end (DND1).
Mouse apolipoprotein B editing complex 3 (APOBEC3) is expressed in germ cells and interacts with dead-end (DND1).
复制标题
DOI：
10.1371/journal.pone.0002315
复制
发表时间：
2008-05-28
期刊：
影响因子：
3.7
通讯作者：
Matin A
中科院分区：
文献类型：
--
作者：
Bhattacharya C;Aggarwal S;Kumar M;Ali A;Matin A
死端（Dnd 1）基因是维持生殖细胞活力所必需的。Dnd 1的失活导致不育和睾丸肿瘤。Dnd 1编码的蛋白质DND 1能够与信使RNA（mRNA）的3′-非翻译区（UTR）结合，以取代与mRNA的微RNA（miRNA）相互作用。因此，DND 1的一个功能是防止miRNA介导的mRNA抑制。我们报告DND 1与APOBEC 3特异性相互作用。APOBEC 3是一种多功能蛋白。它能抑制逆转录病毒的复制。此外，最近的研究表明，APOBEC 3与细胞RNA结合蛋白和mRNA相互作用，以抑制miRNA介导的mRNA抑制。在这里，我们发现DND 1与另一种细胞蛋白APOBEC 3特异性相互作用。我们目前的数据表明，DND 1共免疫沉淀APOBEC 3从哺乳动物细胞和内源性APOBEC 3从小鼠性腺。这两种蛋白质是否直接相互作用仍有待阐明。我们发现DND 1和APOBEC 3都在小鼠胚胎的生殖细胞和早期性腺中表达。荧光标记的DND 1和APOBEC 3的表达表明它们定位于细胞质，并且当DND 1和APOBEC 3在细胞中一起表达时，它们在核周围位点附近隔离。mRNA的3′-UTR通常编码多个miRNA结合位点以及多种RNA结合蛋白的结合位点。根据我们对DND 1-APOBEC 3相互作用的发现，并考虑到DND 1和APOBEC 3与mRNA结合以抑制miRNA介导的抑制的报道，我们的研究暗示DND 1-APOBEC 3相互作用在调节miRNA介导的mRNA抑制中可能起作用。DND 1和APOBEC 3的相互作用可能是维持生殖细胞活力和预防生殖细胞肿瘤发展的一种机制。
The dead-end (Dnd1) gene is essential for maintaining the viability of germ cells. Inactivation of Dnd1 results in sterility and testicular tumors. The Dnd1 encoded protein, DND1, is able to bind to the 3′-untranslated region (UTR) of messenger RNAs (mRNAs) to displace micro-RNA (miRNA) interaction with mRNA. Thus, one function of DND1 is to prevent miRNA mediated repression of mRNA. We report that DND1 interacts specifically with APOBEC3. APOBEC3 is a multi-functional protein. It inhibits retroviral replication. In addition, recent studies show that APOBEC3 interacts with cellular RNA-binding proteins and to mRNA to inhibit miRNA-mediated repression of mRNA. Here we show that DND1 specifically interacts with another cellular protein, APOBEC3. We present our data which shows that DND1 co-immunoprecipitates APOBEC3 from mammalian cells and also endogenous APOBEC3 from mouse gonads. Whether the two proteins interact directly remains to be elucidated. We show that both DND1 and APOBEC3 are expressed in germ cells and in the early gonads of mouse embryo. Expression of fluorescently-tagged DND1 and APOBEC3 indicate they localize to the cytoplasm and when DND1 and APOBEC3 are expressed together in cells, they sequester near peri-nuclear sites. The 3′-UTR of mRNAs generally encode multiple miRNA binding sites as well as binding sites for a variety of RNA binding proteins. In light of our findings of DND1-APOBEC3 interaction and taking into consideration reports that DND1 and APOBEC3 bind to mRNA to inhibit miRNA mediated repression, our studies implicate a possible role of DND1-APOBEC3 interaction in modulating miRNA-mediated mRNA repression. The interaction of DND1 and APOBEC3 could be one mechanism for maintaining viability of germ cells and for preventing germ cell tumor development.
登录
查看更多内容
影响因子：
64.5
作者：
Harris, RS;Bishop, KN;Malim, MH
通讯作者：
Malim, MH
影响因子：
16
作者：
Harris, RS;Petersen-Mahrt, SK;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
4.8
作者：
Lellek, H;Kirsten, R;Greeve, J
通讯作者：
Greeve, J
影响因子：
4.8
作者：
Huang, Jialing;Liang, Zhihui;Zhang, Hui
通讯作者：
Zhang, Hui
影响因子：
64.8
作者：
Esnault, C;Heidmann, O;Schwartz, O
通讯作者：
Schwartz, O