The functional complexity of the RNA-binding protein Yra1: mRNA biogenesis, genome stability and DSB repair

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.