Lindtner Susan, Zolotukhin Andrei S, Uranishi Hiroaki, Bear Jenifer, Kulkarni Viraj, Smulevitch Sergey, Samiotaki Martina, Panayotou George, Felber Barbara K, Pavlakis George N
Human Retrovirus Section.
J Biol Chem. 2006 Dec 1;281(48):36915-28. doi: 10.1074/jbc.M608745200. Epub 2006 Sep 25.
Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
逆转录病毒/逆转录元件提供了一些工具，可用于识别和剖析细胞mRNA转录后调控的基本步骤。在小鼠逆转座子中鉴定出的RNA转运元件（RTE）在功能上等同于D型逆转录病毒的组成型转运元件，但不直接与mRNA输出受体NXF1结合。在此，我们报道RNA结合基序蛋白15（RBM15）在体外能直接且特异性地识别RTE，并在体内刺激含RTE的报告mRNA的输出和表达。将RBM15与报告mRNA拴系表明，RBM15通过促进mRNA从细胞核输出发挥作用。我们还发现RBM15与NXF1结合，并且这两种蛋白在刺激RTE介导的mRNA输出和表达方面相互协作。因此，RBM15是一种新型的mRNA输出因子，并且是NXF1途径的一部分。我们提出，RTE进化为一种高亲和力的RBM15配体，以提供与NXF1的非剪接依赖性连接，从而确保逆转座子转录本的有效核输出和表达。
