SUMO routes ribosome maturation
SUMO routes ribosome maturation
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DOI：
10.4161/nucl.2.6.17604
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发表时间：
2011-11-01
期刊：
影响因子：
3.7
通讯作者：
Muller, Stefan
中科院分区：
文献类型：
--
作者：
Finkbeiner, Elisabeth;Haindl, Markus;Muller, Stefan
核糖体生物发生的控制是一个关键的细胞节点，它保证了蛋白质合成与细胞生长和增殖的协调。在细胞质组装之前，40S和60S核糖体亚基通过成熟途径穿过核核和核质，该途径涉及一组非编码rna和非核糖体调节交易因子。在哺乳动物细胞中，所需蛋白质成分的库存仍然是零碎的，并且在很大程度上不清楚是什么驱动亚细胞转变和沿着成熟途径的蛋白质成分交换。然而，最近的数据表明，泛素样SUMO修饰剂的动态翻译后修饰在这些过程中起关键作用。特别是，SUMO特异性异肽酶SENP3将SUMO从交易因子中去除，有助于哺乳动物的60S成熟途径。为了确定SENP3的相关靶点，我们鉴定了一种由PELP1、TEX10和WDR18组成的新型SENP3相关蛋白复合物。我们证明了该复合物参与了28S rRNA成熟的核仁步骤和随后的60S核糖体亚基的核质转运。重要的是，我们发现PELP1是SUMO的senp3敏感靶点，并且观察到缺乏senp3介导的去氧化可以阻止PELP1- tex10 - wdr18复合物的核仁分配。因此，相扑依赖的亚核运输可能有助于协调核糖体的形成速度。在这里，我们提出PELP1的summoylation作为一种质量控制机制，限制了PELP1- wdr18 - tex10复合物的预成熟装载到60S颗粒，从而限制了核糖体的成熟。我们进一步假设pelp1相关的aaa - atp酶MDN1可能是这一监测途径的一部分。
T he control of ribosome biogenesis is a critical cellular nodal point, which ensures that protein synthesis is coordinated with cell growth and proliferation. Prior to their cytoplasmic assembly the 40S and 60S ribosomal subunits pass through the nucleolus and the nucleoplasm via a maturation pathway that involves a set of non-coding RNAs and non-ribosomal regulatory transacting factors. In mammalian cells the inventory of the required protein components is still fragmentary and it is largely unclear what drives the subcellular transitions and the exchange of protein components along the maturation pathway. However, recent data indicate that the dynamic post-translational modification by the ubiquitin-like SUMO modifier is critically involved in these processes. In particular, removal of SUMO from transacting factors by the SUMO-specific isopeptidase SENP3 is instrumental in the 60S maturation pathway in mammals. In an attempt to pinpoint the relevant targets of SENP3 we identified a novel SENP3-associated protein complex comprised of PELP1, TEX10 and WDR18. We demonstrated that this complex is involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the 60S ribosomal subunit. Importantly, we found that PELP1 is a SENP3-sensitive target of SUMO and observed that lack of SENP3-mediated desumoylation prevents the nucleolar partitioning of the PELP1-TEX10-WDR18 complex. SUMO-dependent subnuclear trafficking may thus assist in coordinating the rate of ribosome formation. Here we propose that sumoylation of PELP1 serves as a quality control mechanism that restricts pre-mature loading of the PELP1-WDR18-TEX10 complex to 60S particles thereby limiting ribosome maturation. We further hypothesize that the PELP1-associated AAA-ATPase MDN1 may be part of this surveillance pathway.