Translation Initiation Site Profiling Reveals Widespread Synthesis of Non-AUG-Initiated Protein Isoforms in Yeast.
Translation Initiation Site Profiling Reveals Widespread Synthesis of Non-AUG-Initiated Protein Isoforms in Yeast.
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DOI：
10.1016/j.cels.2020.06.011
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发表时间：
2020-08-26
期刊：
影响因子：
9.3
通讯作者：
Brar GA
中科院分区：
文献类型：
--
作者：
Eisenberg AR;Higdon AL;Hollerer I;Fields AP;Jungreis I;Diamond PD;Kellis M;Jovanovic M;Brar GA
芽殖酵母的基因组分析有助于确定真核基因表达的基本原则。然而，在缺乏用于定义编码区的经验方法的情况下，这些分析在历史上排除了特定类别的可能编码区，例如在非AUG起始密码子处起始的那些。在这里，我们应用了一种实验方法，在酵母中的翻译起始位点进行全局注释，并确定了149个基因的替代N-末端延伸的蛋白质亚型从近同源密码子上游的注释AUG起始密码子。这些异构体与典型异构体一起产生，并以高特异性翻译，这是由于仅在可能的起始密码子的一小部分处起始。驱动其产生的非AUG起始在减数分裂期间富集并由低eIF 5A诱导，这在此背景下可见。这些发现揭示了非典型蛋白质异构体的广泛生产和意想不到的复杂性，即使是一个简单的真核基因组解码的规则。Eisenberg等人鉴定了芽殖酵母中全基因组的翻译起始位点。他们定义了一类149个基因，这些基因具有在非AUG起始密码子处起始的替代延伸同种型。这些同种型与它们相应的典型同种型一起产生，但通常以较低的丰度产生，并且在减数分裂期间被选择性地诱导。
Genomic analyses in budding yeast have helped define the foundational principles of eukaryotic gene expression. However, in the absence of empirical methods for defining coding regions, these analyses have historically excluded specific classes of possible coding regions, such as those initiating at non-AUG start codons. Here, we applied an experimental approach to globally annotate translation initiation sites in yeast and identified 149 genes with alternative N-terminally extended protein isoforms initiating from near-cognate codons upstream of annotated AUG start codons. These isoforms are produced in concert with canonical isoforms and translated with high specificity, resulting from initiation at only a small subset of possible start codons. The non-AUG initiation driving their production is enriched during meiosis and induced by low eIF5A, which is seen in this context. These findings reveal widespread production of non-canonical protein isoforms and unexpected complexity to the rules by which even a simple eukaryotic genome is decoded. Eisenberg et al. identify translation initiation sites genome-wide in budding yeast. They define a class of 149 genes with alternate extended isoforms that initiate at non-AUG start codons. These isoforms are produced in concert with their corresponding canonical isoforms, but typically at lower abundance, and are selectively induced during meiosis.
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DOI：
10.1261/rna.060541.116
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Celik A;Baker R;He F;Jacobson A
通讯作者：
Jacobson A
影响因子：
7
作者：
Brent, MR
通讯作者：
Brent, MR
影响因子：
64.5
作者：
Cheng Z;Otto GM;Powers EN;Keskin A;Mertins P;Carr SA;Jovanovic M;Brar GA
通讯作者：
Brar GA
影响因子：
4.8
作者：
Chang, KJ;Wang, CC
通讯作者：
Wang, CC
DOI：
10.1016/j.bbrc.2009.01.148
发表时间：
2009-03-20
影响因子：
3.1
作者：
Gregio, Ana P. B.;Cano, Veridiana P. S.;Zanelli, Cleslei F.
通讯作者：
Zanelli, Cleslei F.