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Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast.
Genome research Pub Date : 2019-11-18 , DOI: 10.1101/gr.243378.118
Wu Wei 1, 2, 3 , Bianca P Hennig 4 , Jingwen Wang 5 , Yujie Zhang 5 , Ilaria Piazza 6 , Yerma Pareja Sanchez 5 , Christophe D Chabbert 4 , Sophie H Adjalley 7 , Lars M Steinmetz 3, 4, 8 , Vicent Pelechano 5
Affiliation  

Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site (TSS) usage, chromatin organization, and posttranscriptional consequences in Saccharomyces cerevisiae We show that TSSs of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality, and chromatin accessibility. We define the 5' and 3' boundaries of cryptic transcripts and show that, contrary to RNA degradation-sensitive ones, they often overlap with the end of the gene, thereby using the canonical polyadenylation site, and associate to polyribosomes. We show that chromatin-sensitive cryptic transcripts can be recognized by ribosomes and may produce truncated polypeptides from downstream, in-frame start codons. Finally, we confirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic data sets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters initiates the transcription of alternative truncated mRNA isoforms. The expression of these chromatin-sensitive isoforms is conserved from yeast to human, expanding the functional consequences of cryptic transcription and proteome complexity.

中文翻译:

染色质敏感的隐蔽启动子推定驱动酵母中替代蛋白质同种型的表达。

隐蔽转录广泛存在并产生一组异质的功能未知的 RNA 分子。为了提高我们对隐性转录的理解,我们研究了它们在酿酒酵母中的转录起始位点 (TSS) 使用、染色质组织和转录后结果。我们表明,染色质敏感的内部隐性转录物的 TSS 在 DNA 序列方面保留了与典型 TSS 相当的特征、方向性和染色质可及性。我们定义了隐蔽转录物的 5' 和 3' 边界,并表明,与 RNA 降解敏感转录物相反,它们通常与基因末端重叠,从而使用规范的聚腺苷酸化位点,并与多核糖体相关联。我们表明,染色质敏感的隐蔽转录物可以被核糖体识别,并可能从下游的框内起始密码子产生截短的多肽。最后,我们通过重新分析 N 末端蛋白质组数据集来确认预测多肽的存在。我们的工作表明,一小部分染色质敏感的内部隐蔽启动子启动了替代截短 mRNA 同种型的转录。这些染色质敏感亚型的表达从酵母到人类都是保守的,扩大了隐蔽转录和蛋白质组复杂性的功能后果。我们的工作表明,一小部分染色质敏感的内部隐蔽启动子启动了替代截短 mRNA 同种型的转录。这些染色质敏感亚型的表达从酵母到人类都是保守的,扩大了隐蔽转录和蛋白质组复杂性的功能后果。我们的工作表明,一小部分染色质敏感的内部隐蔽启动子启动了替代截短 mRNA 同种型的转录。这些染色质敏感亚型的表达从酵母到人类都是保守的,扩大了隐蔽转录和蛋白质组复杂性的功能后果。
更新日期:2019-11-01
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