Berlanga Juan José, Baass Alexis, Sonenberg Nahum
Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Québec, Canada.
RNA. 2006 Aug;12(8):1556-68. doi: 10.1261/rna.106506. Epub 2006 Jun 27.
The 5' cap and 3' poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP). Paip2 (PABP-interacting protein 2) binds PABP and inhibits translation both in vitro and in vivo by decreasing the affinity of PABP for polyadenylated RNA. Here, we describe the functional characteristics of Paip2B, a Paip2 homolog. A full-length brain cDNA of Paip2B encodes a protein that shares 59% identity and 80% similarity with Paip2 (Paip2A), with the highest conservation in the two PABP binding domains. Paip2B acts in a manner similar to Paip2A to inhibit translation of capped and polyadenylated mRNAs both in vitro and in vivo by displacing PABP from the poly(A) tail. Also, similar to Paip2A, Paip2B does not affect the translation mediated by the internal ribosome entry site (IRES) of hepatitis C virus (HCV). However, Paip2A and Paip2B differ with respect to both mRNA and protein distribution in different tissues and cell lines. Paip2A is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome. Paip2 protein degradation may constitute a primary mechanism by which cells regulate PABP activity in translation.
真核生物mRNA的5'端帽结构和3'端多聚腺苷酸尾协同作用以增强翻译。这种协同作用是通过真核起始因子4G（eIF4F帽结合复合体的一个组分）与多聚腺苷酸结合蛋白（PABP）之间的相互作用介导的。Paip2（PABP相互作用蛋白2）结合PABP，并通过降低PABP对多聚腺苷酸化RNA的亲和力在体外和体内抑制翻译。在此，我们描述了Paip2的同源物Paip2B的功能特性。Paip2B的全长脑cDNA编码一种与Paip2（Paip2A）具有59%的同一性和80%的相似性的蛋白质，在两个PABP结合结构域中具有最高的保守性。Paip2B在体外和体内通过将PABP从多聚腺苷酸尾上置换下来，以类似于Paip2A的方式抑制加帽和多聚腺苷酸化mRNA的翻译。此外，与Paip2A相似，Paip2B不影响丙型肝炎病毒（HCV）的内部核糖体进入位点（IRES）介导的翻译。然而，Paip2A和Paip2B在不同组织和细胞系中的mRNA和蛋白质分布方面存在差异。Paip2A比Paip2B具有更高的泛素化水平，并且被蛋白酶体降解得更快。Paip2蛋白的降解可能构成细胞在翻译过程中调节PABP活性的主要机制。
