TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules.
TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules.
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TDRD3是一种新型的都铎式结构域的蛋白质，将其定位于细胞质应激颗粒。
DOI：
10.1093/hmg/ddn203
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发表时间：
2008-10-01
影响因子：
3.5
通讯作者：
Cote, Jocelyn
中科院分区：
文献类型：
--
作者：
Goulet, Isabelle;Boisvenue, Sophie;Mokas, Sophie;Mazroui, Rachid;Cote, Jocelyn
我们之前的工作已经证明，“运动神经元存活”蛋白的 Tudor 结构域和含有 Tudor 结构域的蛋白 3（TDRD3）高度相似，并且它们都具有与精氨酸甲基化多肽相互作用的能力。 TDRD3 已被鉴定为过度表达的基因，对雌激素受体阴性乳腺癌的不良预后具有很强的预测价值，但其确切功能仍不清楚。 TDRD3 是一种模块化蛋白，除了其 Tudor 结构域外，它还具有假定的核酸识别基序和泛素相关结构域。我们在此报告，TDRD3 主要定位于细胞质，与脆弱的 X 智力迟钝蛋白共同沉积在主动翻译的多核糖体上。我们还证明 TDRD3 积累成应激颗粒 (SG) 以响应各种细胞应激。引人注目的是，发现 TDRD3 的 Tudor 结构域对于其招募到 SG 来说既是必需的，也是充分的，并且 Tudor 结构域中的甲基结合表面对于这一过程非常重要。 Pull down 实验确定了 5 个新型 TDRD3 相互作用伙伴，其中大多数是潜在甲基化的 RNA 结合蛋白。我们的研究结果表明，其中两种蛋白，SERPINE1 mRNA 结合蛋白 1 和 DEAD/H box-3（仅支持细胞综合征中经常缺失的基因）也是细胞质 SG 的新成分。综上所述，我们报告了 TDRD3 的首次表征及其与至少两种与人类遗传疾病有关的蛋白质的功能相互作用，并提供了支持精氨酸甲基化在 SG 动态调节中的作用的证据。
Our previous work has demonstrated that the Tudor domain of the ‘survival of motor neuron’ protein and the Tudor domain-containing protein 3 (TDRD3) are highly similar and that they both have the ability to interact with arginine-methylated polypeptides. TDRD3 has been identified among genes whose overexpression has a strong predictive value for poor prognosis of estrogen receptor-negative breast cancers, although its precise function remains unknown. TDRD3 is a modular protein, and in addition to its Tudor domain, it harbors a putative nucleic acid recognition motif and a ubiquitin-associated domain. We report here that TDRD3 localizes predominantly to the cytoplasm, where it co-sediments with the fragile X mental retardation protein on actively translating polyribosomes. We also demonstrate that TDRD3 accumulates into stress granules (SGs) in response to various cellular stresses. Strikingly, the Tudor domain of TDRD3 was found to be both required and sufficient for its recruitment to SGs, and the methyl-binding surface in the Tudor domain is important for this process. Pull down experiments identified five novel TDRD3 interacting partners, most of which are potentially methylated RNA-binding proteins. Our findings revealed that two of these proteins, SERPINE1 mRNA-binding protein 1 and DEAD/H box-3 (a gene often deleted in Sertoli-cell-only syndrome), are also novel constituents of cytoplasmic SGs. Taken together, we report the first characterization of TDRD3 and its functional interaction with at least two proteins implicated in human genetic diseases and present evidence supporting a role for arginine methylation in the regulation of SG dynamics.
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影响因子：
4.8
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