A consideration of alternative models for the initiation of translation in eukaryotes.

A consideration of alternative models for the initiation of translation in eukaryotes.
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DOI:
10.3109/10409239209082567
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发表时间:
1992
影响因子:
6.5
通讯作者:
M. Kozak
M. Kozak
中科院分区:
生物学2区
文献类型:
--
作者:
M. Kozak

文献摘要

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虽然最近的生物化学和遗传学研究已经对真核细胞中翻译起始的机制产生了一些见解,但起始过程的两个方面仍然存在争议。一个尚未解决的问题是关于mRNA结合蛋白的各种功能,包括一些起始因子。本文讨论了区分蛋白质与mRNA的特异性和非特异性结合的需要。沿着其他关于mRNA和ATP结合因子功能的观点,对某些起始因子可能作为RNA解旋酶的可能性进行了评价。第二个有争议的问题涉及翻译启动扫描机制的普遍性。根据传统的扫描模型,真核生物核糖体和mRNA之间的初始接触仅发生在信息的5'末端,其通常是加帽的。在一些植物和动物病毒中存在未加帽的mRNA,这促使人们积极寻找其他启动模式。一个“内部启动”机制,首先提出的小核糖核酸病毒,已受到相当大的关注。虽然已经有大量的证据支持这种机制,但许多实验似乎是有缺陷的或不确定的。最后对验证内起爆假说的实验设计提出了一些改进建议。
Although recent biochemical and genetic investigations have produced some insights into the mechanism of initiation of translation in eukaryotic cells, two aspects of the initiation process remain controversial. One unsettled issue concerns a variety of functions that have been proposed for mRNA binding proteins, including some initiation factors. The need to distinguish between specific and nonspecific binding of proteins to mRNA is discussed herein. The possibility that certain initiation factors might act as RNA helicases is evaluated along with other ideas about the functions of mRNA- and ATP-binding factors. A second controversial issue concerns the universality of the scanning mechanism for initiation of translation. According to the conventional scanning model, the initial contact between eukaryotic ribosomes and mRNA occurs exclusively at the 5' terminus of the message, which is usually capped. The existence of uncapped mRNAs among a few plant and animal viruses has prompted a vigorous search for other modes of initiation. An "internal initiation" mechanism, first proposed for picornaviruses, has received considerable attention. Although a large body of evidence has been adduced in support of such a mechanism, many of the experiments appear flawed or inconclusive. Some suggestions are given for improving experiments designed to test the internal initiation hypothesis.