Functional analysis of a random-sequence chromosome reveals a high level and the molecular nature of transcriptional noise in yeast cells.

Functional analysis of a random-sequence chromosome reveals a high level and the molecular nature of transcriptional noise in yeast cells.
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随机序列染色体的功能分析揭示了酵母细胞中转录噪声的高水平和分子性质。

DOI:
10.1016/j.molcel.2023.04.010
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发表时间:
2023
期刊:
影响因子:
16
通讯作者:
Struhl,Kevin
Struhl,Kevin
中科院分区:
生物学1区
文献类型:
--
作者:
Gvozdenov,Zlata;Barcutean,Zeno;Struhl,Kevin

文献摘要

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我们测量转录噪声在酵母中通过分析染色质结构和转录的18 kb区域的DNA序列是随机产生的。核小体完全占据随机序列DNA,但核小体耗尽区(NDRs)的频率要低得多,并且有较少的定位良好的核小体和较短的核小体阵列。随机序列RNA的稳态水平与酵母mRNA相当,尽管转录和衰变速率更高。随机序列DNA的转录起始发生在许多位点,表明RNA Pol II机制的内在特异性非常低。相比之下,随机序列RNA的poly(A)谱与酵母mRNA的poly(A)谱大致相当,表明poly(A)位点选择的进化限制有限。随机序列RNA显示出比酵母mRNA更高的细胞间变异性,这表明功能元件限制了变异性。这些观察结果表明,转录噪音发生在高水平的酵母,他们提供了深入了解染色质和转录模式如何从进化的酵母基因组。
We measure transcriptional noise in yeast by analyzing chromatin structure and transcription of an 18-kb region of DNA whose sequence was randomly generated. Nucleosomes fully occupy random-sequence DNA, but nucleosome-depleted regions (NDRs) are much less frequent, and there are fewer well-positioned nucleosomes and shorter nucleosome arrays. Steady-state levels of random-sequence RNAs are comparable to yeast mRNAs, although transcription and decay rates are higher. Transcriptional initiation from random-sequence DNA occurs at numerous sites, indicating very low intrinsic specificity of the RNA Pol II machinery. In contrast, poly(A) profiles of random-sequence RNAs are roughly comparable to those of yeast mRNAs, suggesting limited evolutionary restraints on poly(A) site choice. Random-sequence RNAs show higher cell-to-cell variability than yeast mRNAs, suggesting that functional elements limit variability. These observations indicate that transcriptional noise occurs at high levels in yeast, and they provide insight into how chromatin and transcription patterns arise from the evolved yeast genome.