通过变构平台重定向SR蛋白的核运输
Redirecting SR Protein Nuclear Trafficking through an Allosteric Platform.
作者信息
Aubol Brandon E, Hailey Kendra L, Fattet Laurent, Jennings Patricia A, Adams Joseph A
机构信息
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA.
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0636, USA.
出版信息
J Mol Biol. 2017 Jul 7;429(14):2178-2191. doi: 10.1016/j.jmb.2017.05.022. Epub 2017 May 31.
Although phosphorylation directs serine-arginine (SR) proteins from nuclear storage speckles to the nucleoplasm for splicing function, dephosphorylation paradoxically induces similar movement, raising the question of how such chemical modifications are balanced in these essential splicing factors. In this new study, we investigated the interaction of protein phosphatase 1 (PP1) with the SR protein splicing factor (SRSF1) to understand the foundation of these opposing effects in the nucleus. We found that RNA recognition motif 1 (RRM1) in SRSF1 binds PP1 and represses its catalytic function through an allosteric mechanism. Disruption of RRM1-PP1 interactions reduces the phosphorylation status of the RS domain in vitro and in cells, redirecting SRSF1 in the nucleus. The data imply that an allosteric SR protein-phosphatase platform balances phosphorylation levels in a "goldilocks" region for the proper subnuclear storage of an SR protein splicing factor.
尽管磷酸化会引导丝氨酸-精氨酸（SR）蛋白从核内储存斑点转移至核质以发挥剪接功能，但去磷酸化却反常地引发类似的转移，这就提出了一个问题：在这些至关重要的剪接因子中，此类化学修饰是如何实现平衡的。在这项新研究中，我们探究了蛋白磷酸酶1（PP1）与SR蛋白剪接因子（SRSF1）之间的相互作用，以了解细胞核中这些相反效应的基础。我们发现，SRSF1中的RNA识别基序1（RRM1）与PP1结合，并通过变构机制抑制其催化功能。RRM1-PP1相互作用的破坏会降低体外和细胞中RS结构域的磷酸化状态，使SRSF1在细胞核中重新分布。这些数据表明，一个变构的SR蛋白-磷酸酶平台在一个“恰到好处”的区域平衡磷酸化水平，以实现SR蛋白剪接因子在细胞核内的适当储存。
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