Transcriptomes of six mutants in the Sen1 pathway reveal combinatorial control of transcription termination across the Saccharomyces cerevisiae genome.

Transcriptomes of six mutants in the Sen1 pathway reveal combinatorial control of transcription termination across the Saccharomyces cerevisiae genome.
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DOI:
10.1371/journal.pgen.1006863
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发表时间:
2017-06
期刊:
影响因子:
4.5
通讯作者:
Brow DA
Brow DA
中科院分区:
生物学2区
文献类型:
--
作者:
Chen X;Poorey K;Carver MN;Müller U;Bekiranov S;Auble DT;Brow DA

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Transcriptome studies on eukaryotic cells have revealed an unexpected abundance and diversity of noncoding RNAs synthesized by RNA polymerase II (Pol II), some of which influence the expression of protein-coding genes. Yet, much less is known about biogenesis of Pol II non-coding RNA than mRNAs. In the budding yeast Saccharomyces cerevisiae, initiation of non-coding transcripts by Pol II appears to be similar to that of mRNAs, but a distinct pathway is utilized for termination of most non-coding RNAs: the Sen1-dependent or “NNS” pathway. Here, we examine the effect on the S. cerevisiae transcriptome of conditional mutations in the genes encoding six different essential proteins that influence Sen1-dependent termination: Sen1, Nrd1, Nab3, Ssu72, Rpb11, and Hrp1. We observe surprisingly diverse effects on transcript abundance for the different proteins that cannot be explained simply by differing severity of the mutations. Rather, we infer from our results that termination of Pol II transcription of non-coding RNA genes is subject to complex combinatorial control that likely involves proteins beyond those studied here. Furthermore, we identify new targets and functions of Sen1-dependent termination, including a role in repression of meiotic genes in vegetative cells. In combination with other recent whole-genome studies on termination of non-coding RNAs, our results provide promising directions for further investigation. The information stored in the DNA of a cell’s chromosomes is transmitted to the rest of the cell by transcribing the DNA into RNA copies or “transcripts”. The fidelity of this process, and thus the health of the cell, depends critically on the proper function of proteins that direct transcription. Since hundreds of genes, each specifying a unique RNA transcript, are arranged in tandem along each chromosome, the beginning and end of each gene must be marked in the DNA sequence. Although encoded in DNA, the signal for terminating an RNA transcript is usually recognized in the transcript itself. We examined the genome-wide functional targets of six proteins implicated in transcription termination by identifying transcripts whose structure or abundance is altered by a mutation that compromises the activity of each protein. For a small minority of transcripts, a mutation in any of the six proteins disrupts termination. Much more commonly, a transcript is affected by a mutation in only one or a few of the six proteins, revealing the varying extent to which the proteins cooperate with one another. We discovered affected transcripts that were not known to be controlled by any of the six proteins, including a cohort of genes required for meiosis.
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发表时间: 2014-11
影响因子: 4.7
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