a Department of Biotechnology , Pondicherry University , Puducherry , India.
b Structural Studies Division , MRC Laboratory of Molecular Biology , Cambridge , UK.
RNA Biol. 2018;15(9):1157-1166. doi: 10.1080/15476286.2018.1517011. Epub 2018 Sep 19.
DDX39B, a DExD RNA helicase, is known to be involved in various cellular processes such as mRNA export, splicing and translation. Previous studies showed that the overexpression of DDX39B promotes the global translation but inhibits the mRNA export in a dominant negative manner. This presents a conundrum as to how DDX39B overexpression would increase the global translation if it inhibits the nuclear export of mRNAs. We resolve this by showing that DDX39B affects the levels of pre-ribosomal RNA by regulating its stability as well as synthesis. Furthermore, DDX39B promotes proliferation and colony forming potential of cells and its levels are significantly elevated in diverse cancer types. Thus, increase in DDX39B enhances global translation and cell proliferation through upregulation of pre-ribosomal RNA. This highlights a possible mechanism by which dysregulation of DDX39B expression could lead to oncogenesis.
DDX39B 是一种 DExD RNA 解旋酶，已知参与多种细胞过程，如 mRNA 输出、剪接和翻译。先前的研究表明，DDX39B 的过表达以显性负性方式促进整体翻译，但抑制 mRNA 输出。这就提出了一个难题，即如果 DDX39B 抑制 mRNA 的核输出，它如何能增加整体翻译。我们通过表明 DDX39B 通过调节其稳定性和合成来影响核糖体前 RNA 的水平来解决这个问题。此外，DDX39B 促进细胞的增殖和集落形成潜力，并且在多种癌症类型中其水平显著升高。因此，DDX39B 的增加通过上调核糖体前 RNA 增强整体翻译和细胞增殖。这突出了 DDX39B 表达失调可能导致癌变的一种可能机制。
