Yeast poly(A)-binding protein Pab1 shuttles between the nucleus and the cytoplasm and functions in mRNA export

Yeast poly(A)-binding protein Pab1 shuttles between the nucleus and the cytoplasm and functions in mRNA export
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DOI:
10.1261/rna.7291205
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发表时间:
2005-04-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Weis, K
Weis, K
中科院分区:
生物学3区
文献类型:
--
作者:
Brune, C;Munchel, SE;Weis, K

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Pab 1是酵母中主要的poly(A)结合蛋白。它是一种多功能蛋白,介导与信使RNA的3 '-poly(A)-尾相关的许多细胞功能。在这里,我们的特点Pab 1作为出口货物的蛋白质出口因子Xpo 1/Crm 1。Pab 1是酵母抽提物中主要的Xpo 1/Crm 1相互作用蛋白,并以RanGTP依赖的方式直接与Xpo 1/Crm 1结合。当Xpo 1/Crm 1的功能受到抑制时,Pab 1在细胞核和细胞质之间快速穿梭,并在细胞核中部分积累。然而,Pab 1也可以通过替代途径输出,该途径依赖于MEX 67-mRNA输出途径。Pab 1的输入由输入受体Kap 108/Sxm 1通过其第四RNA结合结构域中的核定位信号介导。有趣的是,抑制Pab 1的核输入导致mRNA输出的动力学延迟。此外,pab 1缺失菌株的失活性被核外泌体的一种组分5 '-3'核糖核酸外切酶RRP 6中的突变抑制。因此,核Pab 1可能需要有效的mRNA输出,并可能在细胞核中的mRNA的质量控制中发挥作用。
Pab1 is the major poly(A)-binding protein in yeast. It is a multifunctional protein that mediates many cellular functions associated with the 3'-poly(A)-tail of messenger RNAs. Here, we characterize Pab1 as an export cargo of the protein export factor Xpo1/Crm1. Pab1 is a major Xpo1/Crm1-interacting protein in yeast extracts and binds directly to Xpo1/Crm1 in a RanGTP-dependent manner. Pab1 shuttles rapidly between the nucleus and the cytoplasm and partially accumulates in the nucleus when the function of Xpo1/Crm1 is inhibited. However, Pab1 can also be exported by an alternative pathway, which is dependent on the MEX67-mRNA export pathway. Import of Pab1 is mediated by the import receptor Kap108/Sxm1 through a nuclear localization signal in its fourth RNA-binding domain. Interestingly, inhibition of Pab1's nuclear import causes a kinetic delay in the export of mRNA. Furthermore, the inviability of a pab1 deletion strain is suppressed by a mutation in the 5'-3' exoribonuclease RRP6, a component of the nuclear exosome. Therefore, nuclear Pab1 may be required for efficient mRNA export and may function in the quality control of mRNA in the nucleus.