Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Neuron. 2020 Sep 9;107(5):854-863.e6. doi: 10.1016/j.neuron.2020.06.015. Epub 2020 Jul 7.
The xbp-1 mRNA encodes the XBP-1 transcription factor, a critical part of the unfolded protein response. Here we report that an RNA fragment produced from xbp-1 mRNA cleavage is a biologically active non-coding RNA (ncRNA) essential for axon regeneration in Caenorhabditis elegans. We show that the xbp-1 ncRNA acts independently of the protein-coding function of the xbp-1 transcript as part of a dual output xbp-1 mRNA stress response axis. Structural analysis indicates that the function of the xbp-1 ncRNA depends on a single RNA stem; this stem forms only in the cleaved xbp-1 ncRNA fragment. Disruption of this stem abolishes the non-coding, but not the coding, function of the endogenous xbp-1 transcript. Thus, cleavage of the xbp-1 mRNA bifurcates it into a coding and a non-coding pathway; modulation of the two pathways may allow neurons to fine-tune their response to injury and other stresses.
Xbp-1 mRNA 编码 XBP-1 转录因子，是未折叠蛋白反应的关键部分。在这里，我们报告说，xbp-1 mRNA 切割产生的 RNA 片段是秀丽隐杆线虫轴突再生所必需的具有生物活性的非编码 RNA(ncRNA)。我们表明，xbp-1 ncRNA 作为双输出 xbp-1 mRNA 应激反应轴的一部分，独立于 xbp-1 转录本的蛋白编码功能发挥作用。结构分析表明，xbp-1 ncRNA 的功能取决于单个 RNA 茎；该茎仅在切割的 xbp-1 ncRNA 片段中形成。破坏这个茎会使内源性 xbp-1 转录本失去非编码功能，但不会失去编码功能。因此，xbp-1 mRNA 的切割将其分叉为编码和非编码途径；两种途径的调节可能使神经元能够微调其对损伤和其他应激的反应。
