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

几乎所有真核生物的mRNAs都含有一条Poly(A)尾巴，可以增强帽子依赖的翻译。内部核糖体进入位点(IRESS)具有显著的启动翻译的能力，不依赖于5‘端。IRES元件存在于各种病毒的mRNAs中，也在细胞转录本中被发现。最近，我们发现了Poly(A)尾巴在细胞内IRES驱动的c-myc和Bip mRNAs翻译中的一个新功能：它通过一种不同于激活帽依赖翻译的机制来增强他们的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驱动的翻译的调节因子，这表明可能是(A)独特的因子(S)中介(S)这一增强作用。基于下面的证据，我们建议(1)纯化和鉴定这个(这些)因子(S)，(2)鉴定它的功能和它的相互作用伙伴，(3)研究Poly(A)增强细胞IRESS的潜在机制。

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.