Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast

Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast
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染色质敏感的隐性启动子可能驱动酵母中替代蛋白质亚型的表达

DOI:
10.1101/gr.243378.118
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发表时间:
2019-11
期刊:
影响因子:
7
通讯作者:
Vicent Pelechano
Vicent Pelechano
中科院分区:
生物学1区
文献类型:
--
作者:
Wu Wei;Bianca P. Hennig;Jingwen Wang;Yujie Zhang;Ilaria Piazza;Yerma Pareja Sanchez;Christophe D. Chabbert;Sophie H. Adjalley;Lars M. Steinmetz;Vicent Pelechano

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隐藏转录是广泛存在的,并产生一组功能未知的RNA分子。为了提高我们对隐蔽转录的理解,我们研究了它们在酿酒酵母中的转录起始位点(TSS)的使用、染色质组织和转录后后果。我们发现,TSS的染色质敏感的内部隐藏的成绩单保留典型的TSS的DNA序列,方向性和染色质可及性方面的可比功能。我们定义了隐蔽转录物的5′和3′边界,并表明,与RNA降解敏感的转录物相反,它们通常与基因的末端重叠,从而使用典型的多聚腺苷酸化位点,并与多聚核糖体相关联。我们发现,染色质敏感的隐蔽转录物可以被核糖体识别,并可能从下游产生截短的多肽,框内起始密码子。最后,我们通过重新分析N-末端蛋白质组数据集确认了预测多肽的存在。我们的工作表明,一部分染色质敏感的内部隐性启动子启动了替代截短mRNA亚型的转录。这些染色质敏感亚型的表达从酵母到人类是保守的,扩大了隐蔽转录和蛋白质组复杂性的功能后果。
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.
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