A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation
A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation
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DOI：
10.1038/sj.emboj.7601494
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发表时间：
2007-01-24
期刊：
影响因子：
11.4
通讯作者：
Semler, Bert L.
中科院分区：
文献类型：
--
作者：
Bedard, Kristin M.;Daijogo, Sarah;Semler, Bert L.
大量的病毒和细胞mRNA利用帽非依赖性翻译，采用不同于经典翻译起始的机制。帽非依赖性翻译需要非典型的细胞RNA结合蛋白，然而，这些蛋白在核糖体募集和翻译起始中的作用尚未完全了解。这项工作表明，核质SR蛋白，SRp20，内部核糖体进入位点（IRES）介导的病毒RNA翻译的功能。我们发现SRp20与细胞RNA结合蛋白PCBP2相互作用，PCBP2是一种与某些小核糖核酸病毒基因组RNA内的IRES序列结合的蛋白质，是病毒翻译所必需的。我们利用SRp20耗竭的HeLa细胞提取物中的体外翻译来证明SRp20是脊髓灰质炎病毒翻译起始所需的。用短干扰RNA靶向HeLa细胞中的SRp20导致SRp20蛋白表达的抑制和脊髓灰质炎病毒翻译的相应减少。我们的数据已经确定了SR蛋白的一个以前未知的功能（即，IRES介导的翻译的刺激），进一步证明了这类重要的细胞RNA结合蛋白的多功能性质。
A significant number of viral and cellular mRNAs utilize cap-independent translation, employing mechanisms distinct from those of canonical translation initiation. Cap-independent translation requires noncanonical, cellular RNA-binding proteins; however, the roles of such proteins in ribosome recruitment and translation initiation are not fully understood. This work demonstrates that a nucleocytoplasmic SR protein, SRp20, functions in internal ribosome entry site (IRES)-mediated translation of a viral RNA. We found that SRp20 interacts with the cellular RNA-binding protein, PCBP2, a protein that binds to IRES sequences within the genomic RNAs of certain picorna-viruses and is required for viral translation. We utilized in vitro translation in HeLa cell extracts depleted of SRp20 to demonstrate that SRp20 is required for poliovirus translation initiation. Targeting SRp20 in HeLa cells with short interfering RNAs resulted in inhibition of SRp20 protein expression and a corresponding decrease in poliovirus translation. Our data have identified a previously unknown function of an SR protein (i.e., the stimulation of IRES-mediated translation), further documenting the multifunctional nature of this important class of cellular RNA-binding proteins.