Floor Stephen N, Jones Brittnee N, Gross John D
Graduate Group in Biophysics, University of California, San Francisco, California 94158-2517, USA.
RNA Biol. 2008 Oct-Dec;5(4):189-92. doi: 10.4161/rna.6859. Epub 2008 Oct 26.
mRNA decapping by Dcp2 is a critical step in several major eukaryotic mRNA decay pathways. Dcp2 forms the catalytic core of a mRNP that is configured for processing diverse substrates by pathway-specific activators. Here we elaborate a model of catalysis by Dcp2 which posits that activity is controlled by a conformational equilibrium between an open, inactive and closed, active form of the enzyme. Structural studies on yeast Dcp2 indicate that the general activator Dcp1 and substrate promote the closed form of the enzyme. Kinetic studies indicate the catalytic step of decapping is rate-limiting and accelerated by Dcp1. We propose that regulation of conformational transitions in Dcp2 during a rate-limiting step after assembly of the decapping mRNP provides a checkpoint for determining if an mRNA is degraded or recycled to translation.
由Dcp2介导的mRNA去帽是几种主要真核生物mRNA降解途径中的关键步骤。Dcp2构成了一个mRNP的催化核心，该mRNP通过特定途径的激活剂来处理各种底物。在这里，我们阐述了一个由Dcp2介导的催化模型，该模型假定酶的活性受开放的、无活性形式与封闭的、活性形式之间的构象平衡控制。对酵母Dcp2的结构研究表明，通用激活剂Dcp1和底物会促使酶形成封闭形式。动力学研究表明，去帽的催化步骤是限速步骤，且Dcp1会加速该步骤。我们提出，在去帽mRNP组装后的限速步骤中，Dcp2构象转变的调节为确定mRNA是被降解还是被循环用于翻译提供了一个检查点。
