Department of Cell Biology, University of Geneva, 30 Quai E. Ansermet, 1211, Geneva, Switzerland.
Curr Genet. 2020 Feb;66(1):63-71. doi: 10.1007/s00294-019-01011-8. Epub 2019 Jul 10.
The mRNA export adaptor Yra1 is essential in S. cerevisiae, and conserved from yeast to human (ALY/REF). It is well characterized for its function during transcription elongation, 3' processing and mRNA export. Recently, different studies linked Yra1 to genome stability showing that Yra1 overexpression causes DNA Double Strand Breaks through DNA:RNA hybrids stabilization, and that Yra1 depletion affects DSB repair. However, the mechanisms through which Yra1 contributes to genome stability maintenance are not fully understood. Interestingly, our results showed that the Yra1 C-box domain is required for Yra1 recruitment to an HO-induced irreparable DSB following extensive resection, and that it is essential to repair an HO-induced reparable DSB. Furthermore, we defined that the C-box domain of Yra1 plays a crucial role in DSB repair through homologous recombination but not through non-homologous end joining. Future studies aim at deciphering the mechanism by which Yra1 contributes to DSB repair by searching for Yra1 partners important for this process. This review focuses on the functional complexity of the Yra1 protein, not only summarizing its role in mRNA biogenesis but also emphasizing its auto-regulation and implication in genome integrity either through DNA:RNA hybrids stabilization or DNA double strand break repair in S. cerevisiae.
mRNA 输出接头蛋白 Yra1 在酿酒酵母中是必需的，并且从酵母到人类都是保守的（ALY/REF）。它在转录延伸、3'加工和 mRNA 输出过程中的功能已得到很好的描述。最近，不同的研究将 Yra1 与基因组稳定性联系起来，表明 Yra1 过表达通过稳定 DNA:RNA 杂交体导致 DNA 双链断裂，而 Yra1 耗竭会影响 DSB 修复。然而，Yra1 如何有助于维持基因组稳定性的机制尚不完全清楚。有趣的是，我们的结果表明，Yra1 的 C 盒结构域是 Yra1 在广泛切除后招募到 HO 诱导的不可修复 DSB 所必需的，并且对于修复 HO 诱导的可修复 DSB 也是必需的。此外，我们定义了 Yra1 的 C 盒结构域通过同源重组而不是非同源末端连接在 DSB 修复中起着至关重要的作用。未来的研究旨在通过寻找对该过程重要的 Yra1 伴侣来解码 Yra1 促进 DSB 修复的机制。这篇综述重点介绍了 Yra1 蛋白的功能复杂性，不仅总结了它在 mRNA 生物发生中的作用，还强调了它通过 DNA:RNA 杂交体的稳定或 DNA 双链断裂修复在酿酒酵母中对基因组完整性的自动调节和影响。
