Transcription and chromatin-based surveillance mechanism controls suppression of cryptic antisense transcription.
Transcription and chromatin-based surveillance mechanism controls suppression of cryptic antisense transcription.
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DOI：
10.1016/j.celrep.2021.109671
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发表时间：
2021-09-07
期刊：
影响因子：
8.8
通讯作者：
Vasiljeva L
中科院分区：
文献类型：
--
作者：
Heo DH;Kuś K;Grzechnik P;Tan-Wong SM;Birot A;Kecman T;Nielsen S;Zenkin N;Vasiljeva L
RNA聚合酶II C端区Y1S2P3T4S5P6S7共有序列的磷酸化协调转录过程中的关键事件，其去调控导致转录和RNA加工过程中的缺陷。在这里，我们报告了裂解酵母Hos2/Set3复合体的组蛋白去乙酰基酶活性在抑制RNA聚合酶II由于Ssu72磷酸酶丢失而引起的磷酸化失调时抑制反义转录的隐蔽启动方面发挥了重要作用。有趣的是，虽然单独的HOS2和SET3突变体几乎没有影响，但是HOS2或SET3的缺失与SSU72Δ联合导致全球反义转录的协同增加，并与对遗传毒性药物的敏感性增加相关。我们证明了Ssu72/Hos2/Set3机制在抑制最容易受到这些缺陷影响的融合基因3‘端的隐蔽反义转录方面发挥了关键作用，确保了简单真核生物密集基因组中基因表达的保真度。保守的磷酸酶Ssu72控制RNA聚合酶II的磷酸化，Ssu72是转录终止所必需的聚合基因，反义转录在没有Ssu72的情况下是全局增加的，HDAC Hos2在没有Ssu72的情况下可以最大限度地减少反义转录，不必要的反义转录可能对细胞有害。Heo等人。证明保守的RNA聚合酶II磷酸酶Ssu72和组蛋白去乙酰基酶Hos2合作控制来自分裂酵母基因组的隐蔽反义转录。
Phosphorylation of the RNA polymerase II C-terminal domain Y1S2P3T4S5P6S7 consensus sequence coordinates key events during transcription, and its deregulation leads to defects in transcription and RNA processing. Here, we report that the histone deacetylase activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of antisense transcription when RNA polymerase II phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, although single Hos2 and Set3 mutants have little effect, loss of Hos2 or Set3 combined with ssu72Δ results in a synergistic increase in antisense transcription globally and correlates with elevated sensitivity to genotoxic agents. We demonstrate a key role for the Ssu72/Hos2/Set3 mechanism in the suppression of cryptic antisense transcription at the 3′ end of convergent genes that are most susceptible to these defects, ensuring the fidelity of gene expression within dense genomes of simple eukaryotes. Conserved phosphatase Ssu72 controls RNA polymerase II phosphorylation Ssu72 is required for transcription termination at convergent genes Antisense transcription is globally increased in the absence of Ssu72 HDAC Hos2 acts in the absence of Ssu72 to minimize antisense transcription Unwanted antisense transcription might be detrimental for the cell. Heo et al. demonstrate that conserved RNA polymerase II phosphatase Ssu72 and histone deacetylase Hos2 collaborate to keep under control the cryptic antisense transcription that arises from the fission yeast genome.
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DOI：
10.1126/science.aao6535
发表时间：
2017-11-24
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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DOI：
10.1261/rna.065524.118
发表时间：
2018-09
期刊：
RNA (New York, N.Y.)
影响因子：
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通讯作者：
Bähler J
影响因子：
3.7
作者：
Bitton, Danny A.;Schubert, Falk;Baehler, Jureg
通讯作者：
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影响因子：
16
作者：
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通讯作者：
Buratowski, S
影响因子：
16.8
作者：
Austenaa LMI;Piccolo V;Russo M;Prosperini E;Polletti S;Polizzese D;Ghisletti S;Barozzi I;Diaferia GR;Natoli G
通讯作者：
Natoli G