The Polycomb protein and E3 ubiquitin ligase Ring1B harbors an IRES in its highly conserved 5' UTR.

The Polycomb protein and E3 ubiquitin ligase Ring1B harbors an IRES in its highly conserved 5' UTR.
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Polycomb蛋白和E3泛素连接酶环1b在其高度保守的5'UTR中具有IRES。

DOI:
10.1371/journal.pone.0002322
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发表时间:
2008-06-04
期刊:
影响因子:
3.7
通讯作者:
van Lohuizen, Maarten
van Lohuizen, Maarten
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Boutsma, Erwin;Noback, Sonja;van Lohuizen, Maarten

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Ring1B是高度保守的Polycomb蛋白群的重要成员,它通过修饰局部染色质结构来协调发育过程、细胞生长和干细胞命运。Ring1B被发现是单泛素化组蛋白H2A的E3连接酶,这为Polycomb蛋白的染色质修饰增加了一个新的水平。在这里,我们报告了Ring1B属于一组独特的蛋白质,它们的翻译依赖于mRNA中一个稳定的5 ' UTR序列,即内部核糖体进入位点(IRES)。在细胞转染实验中,Ring1B IRES的表达水平明显高于不含IRES的Ring1B cDNA。此外,双荧光素酶测定显示Ring1B IRES具有很强的活性。虽然我们的研究结果表明Ring1B可以在帽依赖性翻译受损的情况下翻译,但我们发现Ring1B IRES是帽依赖性的。这就提出了Ring1B的翻译控制是一个多层过程的可能性,并且在不同的条件下需要维持Ring1B的翻译,这符合其作为PRC1 Polycomb蛋白复合物中组蛋白H2A单泛素化的E3连接酶的重要作用。
Ring1B is an essential member of the highly conserved Polycomb group proteins, which orchestrate developmental processes, cell growth and stem cell fate by modifying local chromatin structure. Ring1B was found to be the E3 ligase that monoubiquitinates histone H2A, which adds a new level of chromatin modification to Polycomb group proteins. Here we report that Ring1B belongs to the exclusive group of proteins that for their translation depend on a stable 5′ UTR sequence in their mRNA known as an Internal Ribosome Entry Site (IRES). In cell transfection assays the Ring1B IRES confers significantly higher expression levels of Ring1B than a Ring1B cDNA without the IRES. Also, dual luciferase assays show strong activity of the Ring1B IRES. Although our findings indicate Ring1B can be translated under conditions where cap-dependent translation is impaired, we found the Ring1B IRES to be cap-dependent. This raises the possibility that translational control of Ring1B is a multi-layered process and that translation of Ring1B needs to be maintained under varying conditions, which is in line with its essential role as an E3 ligase for monoubiquitination of histone H2A in the PRC1 Polycomb protein complex.
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