Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms.
Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms.
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DOI：
10.1016/j.molcel.2010.08.025
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发表时间：
2010-09-10
期刊：
影响因子：
16
通讯作者：
Parker R
中科院分区：
文献类型：
--
作者：
Nissan T;Rajyaguru P;She M;Song H;Parker R
真核mRNA降解通常发生在翻译起始被抑制并且mRNA被靶向脱帽的过程中。在酵母细胞中，Pat 1、Scd 6、Edc 3和Dhh 1都通过未知的机制起促进去帽的作用。我们证明，纯化的Scd 6和一个区域的帕特1直接抑制翻译在体外通过限制形成一个稳定的48 S前起始复合物。此外，虽然Pat 1，Edc 3，Dhh 1和Scd 6都结合脱帽酶，但只有Pat 1和Edc 3增强其活性。我们还确定了Pat 1，Dcp 1，Dcp 2，Dhh 1，Scd 6，Edc 3，Xrn 1和Lsm 1 -7复合物之间的许多直接相互作用。这些观察结果确定了三个类的decapping激活剂，其功能是直接抑制翻译起始和/或刺激Dcp 1/2。此外，帕特1被确定为关键的mRNA衰减，首先抑制翻译起始，然后作为一个支架，招募组件的decapping复合物，并最终激活Dcp 2。
Eukaryotic mRNA degradation often occurs in a process whereby translation initiation is inhibited and the mRNA is targeted for decapping. In yeast cells, Pat1, Scd6, Edc3, and Dhh1 all function to promote decapping by unknown mechanism(s). We demonstrate that purified Scd6 and a region of Pat1 directly repress translation in vitro by limiting the formation of a stable 48S pre-initiation complex. Moreover, while Pat1, Edc3, Dhh1 and Scd6 all bind the decapping enzyme, only Pat1 and Edc3 enhance its activity. We also identify numerous direct interactions between Pat1, Dcp1, Dcp2, Dhh1, Scd6, Edc3, Xrn1, and the Lsm1-7 complex. These observations identify three classes of decapping activators that function either to directly repress translation initiation and/or stimulate Dcp1/2. Moreover, Pat1 is identified as critical in mRNA decay by first inhibiting translation initiation, then serving as a scaffold to recruit components of the decapping complex, and finally activating Dcp2.