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首页> 外文期刊>Molecular and Cellular Biology >The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences.
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The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences.

机译：GCN4 mRNA中5'-近端开放阅读框的正调节功能可以通过异源，短编码序列来模仿。

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摘要

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function.
机译：酵母菌中GCN4表达的翻译控制是由GCN4 mRNA前导序列中存在的多个AUG密码子介导的，每个密码子都启动了一个只有两个或三个密码子的短开放阅读框。在正常生长条件下，需要上游AUG密码子3和4来抑制GCN4的表达。需要AUG密码子1和2来克服氨基酸饥饿条件下的这种抑制。我们显示，AUG密码子1和2的调节功能可以定性地由两个异源上游开放阅读框（URFs）的AUG密码子模仿，其中包含阅读基因PGK和TRP1的起始区域。这些AUG密码子单独存在于mRNA前导物中会抑制GCN4的表达。但是，当它们在AUG密码子3和4的上游插入时，它们会在减压条件下刺激GCN4的表达。这一发现支持了AUG密码子1和2在控制机制中充当翻译起始位点的想法，并进一步表明抑制了AUG的抑制作用。密码子3和4是上游URF 1和2序列翻译的一般结果。一些观察结果表明，AUG密码子3和4是有效的起始位点。然而，当这些序列位于URF 1上游时，这些序列不充当正调控元件。这一结果表明，有效的翻译只是GCN4 mRNA中5'近端URF的重要特性之一。我们建议第二个属性是在翻译终止后允许重新初始化的能力，并且针对该调节功能优化了URF 1。

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