Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data.
Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data.
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DOI：
10.1101/gr.221507.117
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发表时间：
2018-03
期刊：
影响因子：
7
通讯作者：
McManus J
中科院分区：
文献类型：
--
作者：
Spealman P;Naik AW;May GE;Kuersten S;Freeberg L;Murphy RF;McManus J
上游开放阅读框（uORF）位于转录前导序列（5′ UTR）中，是转录和mRNA周转的顺式调节因子。最近的全基因组核糖体分析研究表明，成千上万的uORF起始于非AUG起始密码子。虽然有趣，但这些非AUG uORF预测是在没有统计控制或验证的情况下进行的;因此，这些元素的重要性仍有待证明。为了解决这个问题，我们采用比较基因组学方法来研究AUG和非AUG uORF。我们映射了多个酵母属酵母物种的转录前导序列，并将一种新的机器学习算法（uORF-seqr）应用于核糖体分析数据，以识别统计学上显著的uORFs。我们发现AUG和非AUG uORF都经常在酵母菌中发现。虽然大多数非AUG uORF仅在一个物种中发现，但在酵母属中有数百个具有保守的序列或位置。以UUG起始的uORF特别常见，并且以与AUG uORF相似的速率在物种之间共享。然而，非AUG uORF的翻译效率低于AUG-uORF，并且在正常生长条件下较少通过替代转录起始而被去除。这些结果表明，一个子集的非AUG uORF可能在调控基因表达中发挥重要作用。
Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression.
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影响因子：
7.7
作者：
Andreev DE;O'Connor PB;Fahey C;Kenny EM;Terenin IM;Dmitriev SE;Cormican P;Morris DW;Shatsky IN;Baranov PV
通讯作者：
Baranov PV
影响因子：
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作者：
Hussmann, Jeffrey A.;Patchett, Stephanie;Press, William H.
通讯作者：
Press, William H.
影响因子：
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作者：
Davuluri, RV;Suzuki, Y;Zhang, MQ
通讯作者：
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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。
影响因子：
3
作者：
通讯作者：
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影响因子：
7
作者：
Arribere JA;Gilbert WV
通讯作者：
Gilbert WV