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

机译:酵母聚(A)结合蛋白Pab1在细胞核与细胞质之间穿梭,并在mRNA出口中发挥作用

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摘要

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.
机译:Pab1是酵母中主要的poly(A)结合蛋白。它是一种多功能蛋白,可介导与信使RNA的3'-poly(A)-尾相关的许多细胞功能。在这里,我们将Pab1表征为蛋白质出口因子Xpo1 / Crm1的出口货物。 Pab1是酵母提取物中主要的Xpo1 / Crm1相互作用蛋白,并以RanGTP依赖的方式直接与Xpo1 / Crm1结合。当Xpo1 / Crm1的功能受到抑制时,Pab1在核和细胞质之间快速穿梭,并部分地在核中积累。但是,Pab1也可以通过其他途径输出,该途径取决于MEX67-mRNA出口途径。 Pab1的导入由导入受体Kap108 / Sxm1通过其第四个RNA结合域中的核定位信号介导。有趣的是,抑制Pab1的核输入会导致mRNA输出的动力学延迟。此外,pab1缺失菌株的生存力受到5'-3'外核糖核酸酶RRP6(核外泌体的组成部分)突变的抑制。因此,可能需要核Pab1才能有效地输出mRNA,并且可能在细胞核中mRNA的质量控制中发挥作用。

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