Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in yeast.
Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in yeast.
复制标题
Upf3p 的核输入由输入蛋白-α/-β 介导，并且输出到细胞质是酵母中功能性无义介导的 mRNA 衰减途径所必需的。
DOI：
10.1093/genetics/161.4.1465
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发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Culbertson,MichaelR
中科院分区：
文献类型：
--
作者：
Shirley,ReneeL;Ford,AmandaS;Richards,MRachel;Albertini,Markus;Culbertson,MichaelR
Upf 3 p是酵母中无义介导的mRNA衰变（NMD）所必需的，主要存在于细胞质中，但当UPF 3过表达或upf 3突变阻止核输出时，它会在细胞核内积累。upf 3 p与importin-α（importin-α）相互作用。在温度敏感型rp 1 - 31菌株中，upf 3 p不能进入细胞核，说明upf 3 p进入细胞核是由importin-α/β异源二聚体介导的。Upf 3 p的核输出由富含亮氨酸的核输出序列（NES-A）介导，但输出不依赖于Crm 1 p输出蛋白。在NES-A中鉴定的突变阻止核输出并赋予Nmd表型。将功能性内斯元件添加到输出缺陷的upf-等位基因恢复输出并部分恢复Nmd+表型。我们的研究结果支持了一个模型，其中Upf 3 p在细胞核和细胞质之间的运动是一个功能齐全的NMD通路所必需的。我们还发现Upf 2 p的过表达抑制携带ingnes-A等位基因的突变株的Nmd表型，但对Upf 3 p的定位没有影响。为了解释这些结果，我们认为NES-A中的突变损害了核输出，导致Upf 3 p功能的额外缺陷，这些缺陷不能通过单独恢复输出来纠正。
Upf3p, which is required for nonsense-mediated mRNA decay (NMD) in yeast, is primarily cytoplasmic but accumulates inside the nucleus whenUPF3is overexpressed or whenupf3mutations prevent nuclear export. Upf3p physically interacts with Srp1p (importin-α). Upf3p fails to be imported into the nucleus in a temperature-sensitivesrp1-31strain, indicating that nuclear import is mediated by the importin-α/β heterodimer. Nuclear export of Upf3p is mediated by a leucine-rich nuclear export sequence (NES-A), but export is not dependent on the Crm1p exportin. Mutations identified in NES-A prevent nuclear export and confer an Nmd–phenotype. The addition of a functional NES element to an export-defectiveupf–allele restores export and partially restores an Nmd+phenotype. Our findings support a model in which the movement of Upf3p between the nucleus and the cytoplasm is required for a fully functional NMD pathway. We also found that overexpression of Upf2p suppresses the Nmd–phenotype in mutant strains carryingnes-Aalleles but has no effect on the localization of Upf3p. To explain these results, we suggest that the mutations in NES-A that impair nuclear export cause additional defects in the function of Upf3p that are not rectified by restoration of export alone.