Correct dosage of X chromosome transcription is controlled by a nuclear pore component.
Correct dosage of X chromosome transcription is controlled by a nuclear pore component.
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DOI：
10.1016/j.celrep.2021.109236
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发表时间：
2021-06-15
期刊：
影响因子：
8.8
通讯作者：
Capelson M
中科院分区：
文献类型：
--
作者：
Aleman JR;Kuhn TM;Pascual-Garcia P;Gospocic J;Lan Y;Bonasio R;Little SC;Capelson M
果蝇的剂量补偿涉及雄性X染色体的2倍转录上调，这依赖于X染色体结合的雄性特异性致死（MSL）复合物。然而，这种2倍精度是如何实现的仍不清楚。在这里，我们表明，核孔组件，Mtor，参与设置从男性X染色体转录的正确水平。使用幼虫组织，我们表明，MTOR的耗尽的结果在MSL目标的男性X的选择性上调，超出所需的2倍。Mtor和MSL组分在遗传上相互作用，Mtor的缺失可以挽救MSL组分的雄性致死表型。使用RNA荧光原位杂交（FISH）分析和新生转录测序，我们发现，MTOR的影响是不是由于在mRNA输出的缺陷，但发生在新生转录水平。这些研究结果表明，在剂量补偿的过程中，Mtor的生理作用，作为X染色体基因表达的转录衰减剂。在剂量补偿期间，雄性果蝇的单个X染色体的表达上调以匹配雌性的两个X。Aleman等人表明，核孔蛋白在实现这种转录精确性方面发挥作用，并将雄性X的上调限制在所需的2倍。
Dosage compensation in Drosophila melanogaster involves a 2-fold transcriptional upregulation of the male X chromosome, which relies on the X-chromosome-binding males-specific lethal (MSL) complex. However, how such 2-fold precision is accomplished remains unclear. Here, we show that a nuclear pore component, Mtor, is involved in setting the correct levels of transcription from the male X chromosome. Using larval tissues, we demonstrate that the depletion of Mtor results in selective upregulation at MSL targets of the male X, beyond the required 2-fold. Mtor and MSL components interact genetically, and depletion of Mtor can rescue the male lethality phenotype of MSL components. Using RNA fluorescence in situ hybridization (FISH) analysis and nascent transcript sequencing, we find that the effect of Mtor is not due to defects in mRNA export but occurs at the level of nascent transcription. These findings demonstrate a physiological role for Mtor in the process of dosage compensation, as a transcriptional attenuator of X chromosome gene expression. During dosage compensation, the expression from the single X chromosome of male flies is upregulated to match the two X’s of females. Aleman et al. show that a nuclear pore protein functions in achieving this transcriptional precision and restricts the upregulation of the male X to the required 2-fold.
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