Unrip, a factor implicated in cap-independent translation, associates with the cytosolic SMN complex and influences its intracellular localization
Unrip, a factor implicated in cap-independent translation, associates with the cytosolic SMN complex and influences its intracellular localization
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DOI：
10.1093/hmg/ddi343
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发表时间：
2005-10-15
影响因子：
3.5
通讯作者：
Fischer, U
中科院分区：
文献类型：
--
作者：
Grimmler, M;Otter, S;Fischer, U
剪接体富含尿苷的小核糖核蛋白（U snRNP）组装是由大分子运动神经元（SMN）复合体介导的主动过程。该复合物包含SMN蛋白和六个额外的蛋白质，根据它们在称为gems的核结构中的定位而命名为Gemin 2 -7。在这里，我们提供了另一个存在的生化证据，但非典型的，SMN复杂的组成部分，称为unr相互作用蛋白（unrip）。这种丰富的因子先前已被证明与unr形成复合物，unr是一种参与细胞和病毒mRNA的帽非依赖性翻译的蛋白质。我们表明，unrip是整合到一个复杂的与unr或与SMN复杂的在体内以相互排斥的方式。在后一种情况下，unrip通过与Gemin 7的稳定相互作用被募集到活性SMN复合物中。然而，与SMN和Gemins不同，unrip主要定位于细胞质，并且不存在于gems/Cajal小体中。有趣的是，RNAi诱导的unrip蛋白水平的降低导致SMN在细胞核中的积累增加，这通过核宝石/Cajal小体的形成增加而明显。我们的数据确定unrip作为第一个组件的U snRNP组装机械相关联的SMN复杂的隔室特定的方式。我们推测unrip在SMN复合物的细胞内分布中起着至关重要的作用。
Spliceosomal Uridine-rich small ribonucleo protein (U snRNP) assembly is an active process mediated by the macromolecular survival motor neuron (SMN) complex. This complex contains the SMN protein and six additional proteins, named Gemin2-7, according to their localization to nuclear structures termed gems. Here, we provide biochemical evidence for the existence of another, yet atypical, SMN complex component, termed unr-interacting protein (unrip). This abundant factor has been previously shown to form a complex with unr, a protein implicated in cap-independent translation of cellular and viral mRNA. We show that unrip is integrated into a complex with unr or with the SMN complex in vivo in a mutually exclusive manner. In the latter case, unrip is recruited to the active SMN complex via a stable interaction with Gemin7. However, unlike SMN and Gemins, unrip localizes predominantly to the cytoplasm and is absent from gems/Cajal bodies. Interestingly, RNAi-induced reduction of unrip protein levels leads to enhanced accumulation of SMN in the nucleus as evident by the increased formation of nuclear gems/Cajal bodies. Our data identify unrip as the first component of the U snRNP assembly machinery that associates with the SMN complex in a compartment-specific way. We speculate that unrip plays a crucial role in the intracellular distribution of the SMN complex.