PAB1 self-association precludes its binding to Poly(A), thereby accelerating CCR4 deadenylation in vivo
PAB1 self-association precludes its binding to Poly(A), thereby accelerating CCR4 deadenylation in vivo
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DOI：
10.1128/mcb.00734-07
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发表时间：
2007-09-01
影响因子：
5.3
通讯作者：
Denis, Clyde L.
中科院分区：
文献类型：
--
作者：
Yao, Gang;Chiang, Yueh-Chin;Denis, Clyde L.
已知由CCR 4去腺苷酶催化的mRNA去腺苷化过程是控制酿酒酵母中mRNA降解速率的主要因素。我们已经确定了多聚腺苷酸结合蛋白（PAB 1）的富含脯氨酸的区域和RRM 1结构域是CCR 4去腺苷化所必需的。这些区域中的任一个而不是PAB 1的其他区域的缺失显著降低PAB 1-PAB 1蛋白相互作用，表明PAB 1寡聚化是去腺苷化所需的步骤。此外，这两个区域中的缺陷抑制了在不存在poly（A）的情况下形成的新型环状单体PAB 1物质的形成。PAB 1 RRM 3结构域的去除促进了PAB 1寡聚化和环化，相应地加速了CCR 4去腺苷化。环状PAB 1不能结合poly（A），PABI多聚体严重缺陷或不能结合poly（A），这表明PAB 1 RNA结合表面在进行允许PABI自缔合的接触中至关重要。这些结果支持这样的模型，即体内CCR 4去腺苷化的控制部分地通过在其自缔合成多聚体和/或环状物质后从聚（A）尾去除PABI而发生。因此，不同PAB蛋白的P结构域的已知改变以及影响PABI自缔合的因素和条件将被预期对控制细胞中的mRNA周转至关重要。
The mRNA deadenylation process, catalyzed by the CCR4 deadenylase, is known to be the major factor controlling mRNA decay rates in Saccharomyces cerevisiae. We have identified the proline-rich region and RRM1 domains of poly(A) binding protein (PAB1) as necessary for CCR4 deadenylation. Deletion of either of these regions but not other regions of PAB1 significantly reduced PAB1-PAB1 protein interactions, suggesting that PAB1 oligomerization is a required step for deadenylation. Moreover, defects in these two regions inhibited the formation of a novel, circular monomeric PAB1 species that forms in the absence of poly(A). Removal of the PAB1 RRM3 domain, which promoted PAB1 oligomerization and circularization, correspondingly accelerated CCR4 deadenylation. Circular PAB1 was unable to bind poly(A), and PABI multimers were severely deficient or unable to bind poly(A), implicating the PAB1 RNA binding surface as critical in making contacts that allow PABI self-association. These results support the model that the control of CCR4 deadenylation in vivo occurs in part through the removal of PABI from the poly(A) tail following its self-association into multimers and/or a circular species. Known alterations in the P domains of different PAB proteins and factors and conditions that affect PABI self-association would, therefore, be expected to be critical to controlling mRNA turnover in the cell.