Understanding a Novel Function of the poly(A) Tail in IRES-Mediated Translation of Cellular mRNAs

了解 Poly(A) 尾在 IRES 介导的细胞 mRNA 翻译中的新功能

• 批准号: 12446981
• 负责人: Professor Dr. Matthias Hentze
• 金额: --
• 依托单位: Europäisches Laboratorium für Molekularbiologie (EMBL)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/12446981?language=en
• 关键词: Understanding; Novel; Function; poly; Tail

Almost all eukaryotic mRNAs harbor a poly(A) tail which enhances cap dependent translation. Internal ribosomal entry sites (IRESs) have the remarkable ability to initiate translation independent of the capped 5¿ end. IRES elements are present in a variety of viral mRNAs and have also been identified in cellular transcripts. Recently, we discovered a new function of the poly(A) tail in cellular IRES-driven translation of the c-myc and BiP mRNAs: it enhances their IRES-driven translation by a mechanism that is distinct from how it activates cap-dependent translation. We obtained direct evidence that PABP is not the mediator of the poly (A) contribution to cellular IRES-driven translation indicating the possibility that (a) distinct factor(s) mediate(s) this enhancer function. Based on evidence outlined below, we propose to (1) purify and identify this (these) factor(s), (2) characterize its (their) function and its (their) interacting partners, and (3) investigate the underlying mechanism of the poly(A) enhancement of cellular IRESs.

几乎所有的真核生物mRNA都含有一个poly（A）尾，它可以增强帽依赖性翻译。内部核糖体进入位点（IRES）具有不依赖于加帽的5 ′端启动翻译的显著能力。IRES元件存在于多种病毒mRNA中，并且也已在细胞转录物中鉴定。最近，我们发现了poly（A）尾在c-myc和BiP mRNA的细胞IRES驱动翻译中的新功能：它通过一种与其如何激活帽依赖性翻译不同的机制增强其IRES驱动的翻译。我们获得的直接证据表明PABP不是poly（A）对细胞IRES驱动的翻译的贡献的介导剂，表明不同因子介导这种增强子功能的可能性。基于以下概述的证据，我们建议（1）纯化和鉴定这种（这些）因子，（2）表征其（它们）功能及其（它们）相互作用伴侣，（3）研究poly（A）增强细胞IRES的潜在机制。