Spriggs K A, Mitchell S A, Willis A E
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Biochem Soc Trans. 2005 Dec;33(Pt 6):1483-6. doi: 10.1042/BST0331483.
Most eukaryotic translation initiation is thought to be dependent on the 5'-cap structure of the mRNA. It is becoming apparent, however, that the mRNAs of many genes contain IRESs (internal ribosome entry segments) within the 5'-UTR (5'-untranslated region) that allow ribosomes to initiate translation independently of the 5'-cap. IRESs can enable the expression of these genes under conditions (such as viral infection, cellular stress and apoptosis) when cap-dependent translation initiation is compromised, and also provide a target for regulation of gene expression. Recent results from our laboratory and others suggest that 10% of mRNAs (approximately 4000 genes) use this mechanism to initiate translation. One of the central goals of those working in the field of translation is to identify the sequence motif(s) and proteins that are required for internal ribosome entry. We have identified recently a unique PTB (polypyrimidine tract-binding protein) motif (CCU)n that is present in a large subset of cellular IRESs, and the results suggest that PTB itself is involved either directly or indirectly in ribosome recruitment. Here, we describe further investigations of PTB with artificial sequences that harbour this motif.
大多数真核生物的翻译起始被认为依赖于mRNA的5'-帽结构。然而，越来越明显的是，许多基因的mRNA在5'-非翻译区（5'-UTR）内含有内部核糖体进入片段（IRES），这些片段可使核糖体独立于5'-帽起始翻译。当帽依赖性翻译起始受损时，IRES能够在诸如病毒感染、细胞应激和凋亡等条件下使这些基因得以表达，并且还为基因表达调控提供了一个靶点。我们实验室和其他研究机构最近的结果表明，10%的mRNA（约4000个基因）利用这种机制起始翻译。翻译领域研究人员的核心目标之一是确定内部核糖体进入所需的序列基序和蛋白质。我们最近鉴定出一个独特的富含嘧啶区域结合蛋白（PTB）基序（CCU）n，它存在于大量细胞IRES的一个子集中，结果表明PTB本身直接或间接参与核糖体募集。在此，我们描述了对带有该基序的人工序列进行的PTB进一步研究。
