Mammalian L1 retrotransposon - host interaction

最新调查结果： L1和它的宿主是如何相互作用的，这在很大程度上是未知的。我们研究了两个可能的例子：(1)ORF1p-ORF1p，两个L1编码蛋白之一，在最近的灵长类历史中经历了适应性进化(Boissinot等人，Mol)。比奥尔。埃沃尔。18：2186)。适应性进化可以反映生物上的相互作用(例如，病毒与其宿主之间的相互作用)。虽然酵母和哺乳动物的双杂交实验都表明一些宿主蛋白与ORF1p相互作用，但我们发现这些宿主蛋白在进化过程中都是高度保守的。因此，这些宿主蛋白可能不是ORF1p适应性进化的目标。我们现在正在追寻ORF1p适应性反应的其他“目标”。 (2)L1RNA转运-其他研究表明，核交换因子(Nxf1)与L1RNA的一个区域结合。Nxf1是一种宿主蛋白，负责穿梭RNA进出细胞核。我们的进化分析表明，灵长类动物L1-Nxf1结合位点(部分不编码蛋白质)在L1-进化过程中高度保守。然而，与玛丽-路易丝·哈马舍尔德合作的广泛实验现在表明，Nxf1不会重复地影响L1 RNA的运输。因此，我们已经停止了这一部分的项目。

RECENT FINDINGS: How L1 & its host interact it largely unknown. We examined two possible examples: (1) Adaptive evolution of ORF1p - ORF1p, one of two L1 encoded proteins, underwent adaptive evolution in recent primate history (Boissinot, et al, Mol. Biol. Evol. 18: 2186) . Adaptive evolution can reflect a biological interaction (e.g., as between a virus & its host). Although both yeast and mammalian two-hybrid assays showed that some host proteins interact with ORF1p, we showed that these host proteins are all highly conserved during evolution. Thus, these host proteins are not the likely target of the adaptive evolution of ORF1p. We are now pursuing other "targets" of the adaptive response of ORF1p. (2) L1 RNA transport - Others showed that the nuclear exchange factor (NXF1) binds a region of L1 RNA. NXF1 is a host protein that shuttles RNAs in & out of the nucleus. Our evolutionary analysis showed that the L1 NXF1-binding site (part of which does not encode protein) has been highly conserved over 60 Myr of L1-evolution in primates. However, extensive experiments in collaboration with Marie-Louise Hammarskjld now show that NXF1 does NOT reproducibly affect L1 RNA transport. Therefore, we have discontinued this portion of the project.