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Transcriptional and translational mechanisms contribute to regulate the expression of Discs Large 1 protein during different biological processes

机译：转录和翻译机制有助于调节Discs Large 1蛋白在不同生物学过程中的表达

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摘要

Human discs large (DLG1) has been demonstrated to be involved in cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 expression are not fully understood. This is relevant as DLG1 is lost during the later stages of malignant progression. We initiated a series of studies to analyse the mechanisms regulating DLG1 expression. We have previously reported the identification of an alternative splicing event in the 5' untranslated region (5'-UTR) of DLG1 mRNA that generates transcripts with two different 5'-UTR (short and large 5'-UTR variants). In this study, we further examined the impact of the DLG1 transcription and the role of the differential expression of the alternative 5'-UTRs on DLG1 protein levels. We analysed these mechanisms during cell processes like differentiation, cell cycle progression and cell-cell contact formation, where the importance of DLG1 activities was previously established. The data presented in this report suggest that the transcriptional regulation of DLG1 strongly contributes to DLG1 abundance and that differential expression of alternative 5'-UTRs with different translational properties, also cooperates, depending on the cell type and cell situation. This study provides new evidence for understanding the transcriptional regulation of DLG1 and the changes in DLG1 expression during different biological processes.
机译：大圆盘（DLG1）已被证明参与细胞极性和组织结构的维持。但是，控制DLG1表达的机制尚未完全了解。这与DLG1在恶性进展的后期阶段丢失有关。我们发起了一系列研究，以分析调节DLG1表达的机制。我们先前已经报道了在DLG1 mRNA的5'非翻译区（5'-UTR）中产生另一种剪接事件的鉴定，该事件会生成带有两个不同5'-UTR（短和大5'-UTR变体）的转录本。在这项研究中，我们进一步检查了DLG1转录的影响以及替代5'-UTR差异表达对DLG1蛋白质水平的作用。我们分析了细胞过程中的这些机制，如分化，细胞周期进程和细胞间接触形成，其中先前确定了DLG1活性的重要性。该报告中提供的数据表明，DLG1的转录调控强烈促进了DLG1的丰度，并且取决于细胞类型和细胞状况，具有不同翻译特性的替代5'-UTR的差异表达也可以协同工作。这项研究为理解DLG1的转录调控以及不同生物学过程中DLG1表达的变化提供了新的证据。

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