Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants
Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants
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DOI：
10.1016/j.gene.2015.07.030
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发表时间：
2015-11-15
期刊：
影响因子：
3.5
通讯作者：
Magnani, Mauro
中科院分区：
文献类型：
--
作者：
Bianchi, Marzia;Giacomini, Elisa;Magnani, Mauro
泛素（Ub）是一种由76个氨基酸组成的小蛋白，参与细胞内许多不同的途径，包括蛋白质周转。在蛋白毒性应激期间，当清除受损/错误折叠蛋白的需求强烈增加时，细胞激活Ub基因转录以面对额外泛素的需要。本文显示了四个泛素编码基因（UBB，UBC，UBA 52，RPS 27 A）在基础和应激条件下对泛素RNA库的贡献。我们的研究结果表明，UBC和RPS 27 A代表的Ub转录组在不同的细胞系的主要部分，但当转换为编码潜力，多聚泛素基因UBC和UBB主要有助于确定细胞内的泛素含量在基础条件下。多聚泛素基因UBB和UBC都在蛋白酶体抑制和氧化应激后上调，其中UBC启动子的响应明显更高。在热应激细胞中检测到类似的输出，具有较低的倍数诱导，其中UBC作为耐热性的主要贡献者。相比之下，在这些应激物下，UBA 52和RPS 27 A mRNA的水平保持不变。值得注意的是，紫外线照射不能诱导Ub基因转录，而是似乎在转录后水平上起作用，通过在紫外线剂量下稳定泛素mRNA，从而诱导其他RNA分子的快速降解。此外，UBC核心启动子包含多个转录起始位点及其对应激反应的证据在这里首次报道。(C)2015爱思唯尔B. V.保留所有权利。
Ubiquitin (Ub) is a small 76-amino acid protein that is engaged in many different pathways within the cell, including protein turnover. During proteotoxic stress, when the demand of clearing damaged/misfolded proteins strongly increases, cells activate Ub gene transcription to face the need of extra ubiquitin. This paper shows the contribution of the four ubiquitin coding genes (UBB, UBC, UBA52, RPS27A) to the ubiquitin RNA pool under basal and stressful conditions. Our results reveal that UBC and RPS27A represent the major fraction of the Ub transcriptome in different cell lines, but when converted to the coding potential, polyubiquitin genes UBC and UBB mainly contribute to determine the intracellular ubiquitin content under basal conditions. Both the polyubiquitin genes UBB and UBC are upregulated upon proteasome inhibition and oxidative stress, with markedly higher responses from the UBC promoter. A similar output, with lower fold-inductions, is detected in heat-stressed cells, with UBC acting as the main contributor to thermotolerance. By contrast, upon these stressors, the levels of UBA52 and RPS27A mRNAs remain unchanged. Remarkably, UV irradiation fails to induce Ub gene transcription, but rather seems to act at the post-transcriptional level, by stabilizing ubiquitin mRNAs at UV doses which induce rapid degradation of other RNA molecules. Moreover, the evidence that the UBC core promoter contains multiple transcription start sites and their responsiveness to stress, is here reported for the first time. (C) 2015 Elsevier B.V. All rights reserved.