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游离的聚腺苷酸(poly(A))通过真核起始因子4G(eIF4G)与聚腺苷酸结合蛋白的相互作用在体外刺激加帽mRNA的翻译。

Free poly(A) stimulates capped mRNA translation in vitro through the eIF4G-poly(A)-binding protein interaction.

作者信息

Borman Andrew M, Michel Yanne M, Malnou Cecile E, Kean Katherine M

机构信息

Unité Postulante de Régulation de la Traduction Eucaryote et Virale, CNRS URA 1966, Institut Pasteur, Paris, France.

出版信息

J Biol Chem. 2002 Sep 27;277(39):36818-24. doi: 10.1074/jbc.M205065200. Epub 2002 Jul 22.

Abstract

The 5' cap and 3' poly(A) tail of classical eukaryotic mRNAs functionally communicate to synergistically enhance translation initiation. Synergy has been proposed to result in part from facilitated ribosome recapture on circularized mRNAs. Here, we demonstrate that this is not the case. In poly(A)-dependent, ribosome-depleted rabbit reticulocyte lysates, the addition of exogenous poly(A) chains of physiological length dramatically stimulated translation of a capped, nonpolyadenylated mRNA. When the poly(A):RNA ratio approached 1, exogenous poly(A) stimulated translation to the same extent as the presence of a poly(A) tail at the mRNA 3' end. In addition, exogenous poly(A) significantly improved translation of capped mRNAs carrying short poly(A(50)) tails. Trans stimulation of translation by poly(A) required the eIF4G-poly(A)-binding protein interaction and resulted in increased affinity of eIF4E for the mRNA cap, exactly as we recently described for cap-poly(A) synergy. These results formally demonstrate that mRNA circularization per se is not the cause of cap-poly(A) synergy at least in vitro.

摘要

经典真核生物mRNA的5'帽和3'聚腺苷酸尾巴在功能上相互作用,协同增强翻译起始。有人提出,协同作用部分源于核糖体在环化mRNA上更容易重新捕获。在这里,我们证明情况并非如此。在依赖聚腺苷酸、去除核糖体的兔网织红细胞裂解物中,添加生理长度的外源聚腺苷酸链可显著刺激带帽的非聚腺苷酸化mRNA的翻译。当聚腺苷酸与RNA的比例接近1时,外源聚腺苷酸刺激翻译的程度与mRNA 3'端存在聚腺苷酸尾巴时相同。此外,外源聚腺苷酸显著改善了携带短聚腺苷酸(50)尾巴的带帽mRNA的翻译。聚腺苷酸对翻译的反式刺激需要eIF4G-聚腺苷酸结合蛋白相互作用,并导致eIF4E对mRNA帽的亲和力增加,正如我们最近描述的帽-聚腺苷酸协同作用一样。这些结果正式证明,至少在体外,mRNA环化本身不是帽-聚腺苷酸协同作用的原因。

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