Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Biochem Biophys Res Commun. 2013 Oct 18;440(2):306-11. doi: 10.1016/j.bbrc.2013.09.068. Epub 2013 Sep 21.
Protein phosphorylation and dephosphorylation are both important for multiple steps in the splicing pathway. Members of the PP1 and PP2A subfamilies of phospho-serine/threonine phosphatases play essential but redundant roles in the second step of the splicing reaction. PP6, a member of the PP2A subfamily, is the mammalian homolog of yeast Sit4p and ppe1, which are involved in cell cycle regulation; however, the involvement of PP6 in the splicing pathway remains unclear. Here we show that PP2A family members physically associate with the spliceosome throughout the splicing reaction. PP2A holoenzyme and PP6 were found stably associated with U1 snRNP. Together our findings indicate that these phosphatases regulate splicing catalysis involving U1 snRNP and suggest an important evolutionary conserved role of PP2A family phosphatases in pre-mRNA splicing.
蛋白质的磷酸化和去磷酸化对于剪接途径的多个步骤都非常重要。PP1 和 PP2A 亚家族的磷酸丝氨酸/苏氨酸磷酸酶成员在剪接反应的第二步中发挥着重要但冗余的作用。PP6 是 PP2A 亚家族的成员，是酵母 Sit4p 和 ppe1 的哺乳动物同源物，它们参与细胞周期调控；然而，PP6 参与剪接途径的情况尚不清楚。在这里，我们表明 PP2A 家族成员在整个剪接反应中与剪接体物理结合。发现 PP2A 全酶和 PP6 与 U1 snRNP 稳定结合。我们的研究结果表明，这些磷酸酶调节涉及 U1 snRNP 的剪接催化，并提示 PP2A 家族磷酸酶在 pre-mRNA 剪接中具有重要的进化保守作用。
