Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation.
Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation.
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使用启发式和进化保护鉴定酵母基因组中推定的调节性上游ORF。
DOI：
10.1186/1471-2105-8-295
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发表时间：
2007-08-08
影响因子：
3
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mRNA的翻译效率可以通过存在于某些基因中的上游开放阅读框（uORF）来调节。uORF可以通过干扰主要起始密码子处的翻译再起始来减弱主要ORF的翻译。uORF也偶然出现在基因组中，在这种情况下，它们不具有调节作用。由于功能性uORF的序列决定簇尚不清楚，因此很难通过序列分析区分功能性uORF和假uORF。我们已经使用比较基因组学，以确定新的uORF在酵母中具有很高的可能性，具有翻译调控作用。我们研究了uORF，以前被证明在酿酒酵母的翻译调控中发挥作用，在7个酵母属物种的进化保守。对这组保守的uORF的检查产生了以下三个可用于区分功能性uORF和假uORF的特征：长度在4和6个密码子之间，与主ORF的起始处的距离在50和150个核苷酸之间，以及最后与相邻uORF缺乏重叠和清楚分离。这些衍生的规则与具有类似于GCN 4基因座的性质的uORF固有地相关联，并且可能无法检测其他类型的大多数uORF。基于这些规则具有高得分的uORF显示出比随机选择的uORF高得多的进化保守性。在S.在酿酒酵母中，我们从32个基因中发现了34个保守的uORF，我们预测这些基因是有功能的;随后的分析表明，这些基因中的大多数位于转录本内。共有252个基因被发现含有保守的uORF与属性指示的功能作用，所有，但7个是新的。功能内容分析，这套确定了过度表达的基因参与转录控制和发展。酵母中uORF的进化保守可以追溯到1亿年的分离。保守的uORF在长度、彼此之间的距离以及与主要起始密码子的距离、以及序列的折叠能方面具有某些特征。这些新发现的特征可用于促进其他保守的uORF的检测。
The translational efficiency of an mRNA can be modulated by upstream open reading frames (uORFs) present in certain genes. A uORF can attenuate translation of the main ORF by interfering with translational reinitiation at the main start codon. uORFs also occur by chance in the genome, in which case they do not have a regulatory role. Since the sequence determinants for functional uORFs are not understood, it is difficult to discriminate functional from spurious uORFs by sequence analysis. We have used comparative genomics to identify novel uORFs in yeast with a high likelihood of having a translational regulatory role. We examined uORFs, previously shown to play a role in regulation of translation in Saccharomyces cerevisiae, for evolutionary conservation within seven Saccharomyces species. Inspection of the set of conserved uORFs yielded the following three characteristics useful for discrimination of functional from spurious uORFs: a length between 4 and 6 codons, a distance from the start of the main ORF between 50 and 150 nucleotides, and finally a lack of overlap with, and clear separation from, neighbouring uORFs. These derived rules are inherently associated with uORFs with properties similar to the GCN4 locus, and may not detect most uORFs of other types. uORFs with high scores based on these rules showed a much higher evolutionary conservation than randomly selected uORFs. In a genome-wide scan in S. cerevisiae, we found 34 conserved uORFs from 32 genes that we predict to be functional; subsequent analysis showed the majority of these to be located within transcripts. A total of 252 genes were found containing conserved uORFs with properties indicative of a functional role; all but 7 are novel. Functional content analysis of this set identified an overrepresentation of genes involved in transcriptional control and development. Evolutionary conservation of uORFs in yeasts can be traced up to 100 million years of separation. The conserved uORFs have certain characteristics with respect to length, distance from each other and from the main start codon, and folding energy of the sequence. These newly found characteristics can be used to facilitate detection of other conserved uORFs.