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Abstract：
Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harboring premature stop-codons or short upstream open reading frame (uORFs). Our transcription start sites (TSSs) analysis of Saccharomyces cerevisiae cells deficient for RNA degradation pathways revealed that about half of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spurious transcripts that escaped degradation in the nucleus. Moreover, we found that the low specificity of RNA polymerase II TSSs selection generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or starting downstream of the ATG START codon. Despite the low abundance of this last category of isoforms, their presence seems to constrain genomic sequences, as suggested by the significant bias against in-frame ATGs specifically found at the beginning of the corresponding genes and reflected by a depletion of methionines in the N-terminus of the encoded proteins.
摘要：
无义介导的mRNA衰变（NMD）是一种依赖翻译的RNA质量控制途径，靶向转录本，例如带有过早终止密码子或短上游开放阅读框（uORF）的信使RNA。我们对缺乏RNA降解途径的酿酒酵母细胞的转录起始位点（TSS）分析显示，大约一半的普遍转录本被NMD降解，它提供了一种故障安全机制来去除在细胞核中逃脱降解的假转录本。此外，我们发现RNA聚合酶II的低特异性TSSs选择产生，对于47%的表达基因，携带uORF或在ATG开始密码子下游起始的NMD敏感转录同种型。尽管这最后一类同工型的丰度很低，它们的存在似乎限制了基因组序列，正如在相应基因的开头特别发现的针对框内ATG的显着偏见所表明的那样，并反映在编码蛋白的N端蛋氨酸的消耗中。
