High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection.
High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection.
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DOI：
10.1261/rna.060541.116
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Jacobson A
中科院分区：
文献类型：
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作者：
Celik A;Baker R;He F;Jacobson A
无义介导的mRNA衰变（NMD）在真核生物基因表达中起着重要作用，但NMD靶向转录本的范围和定义特征仍不清楚。为了解决这些问题，我们重新评估了在UPF 1，UPF 2或UPF 3基因缺失的酵母细胞中注释转录本的全基因组表达。我们新的RNA-seq分析证实了先前的微阵列研究结果，但也发现了数百种新的NMD调节的转录本，这些转录本逃过了先前的检测，包括许多含有内含子的前mRNA和几种非编码RNA。绝大多数NMD调控的转录物是外观正常的蛋白质编码mRNA。我们的生物信息学分析显示，这组NMD调控的转录本通常具有较低的翻译效率和较高的框外翻译比率。NMD调控的转录物也具有较低的平均密码子最优性得分和较高的向非最优密码子的转移概率。总的来说，我们的研究结果产生了一个全面的目录酵母NMD基板，并产生新的见解，这些转录的NMD靶向的机制。
Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency and higher ratios of out-of-frame translation. NMD-regulated transcripts also have lower average codon optimality scores and higher transition probability to nonoptimal codons. Collectively, our results generate a comprehensive catalog of yeast NMD substrates and yield new insights into the mechanisms by which these transcripts are targeted by NMD.