Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2
Nuclear export of ribosomal 60S subunits by the general mRNA export receptor Mex67-Mtr2
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DOI：
10.1016/j.molcel.2007.02.018
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发表时间：
2007-04-13
期刊：
影响因子：
16
通讯作者：
Hurt, Ed
中科院分区：
文献类型：
--
作者：
Yao, Wei;Roser, Daniela;Hurt, Ed
酵母Mex 67-Mtr 2复合物及其同源后生动物对应物TAP-p15通过结合和易位mRNA通过核孔复合物作为核输出受体。在这里，我们展示了Mex 67-Mtr 2如何在核糖体60 S亚基的核输出中发挥作用。生物化学和遗传学研究揭示了Mex 67-Mtr 2异源二聚体的NTF 2样支架上先前未被识别的相互作用表面，其在体内结合到前60 S颗粒，并且在体外可以与5S rRNA相互作用。该结合平台的关键结构要求是在Mex 67和Mtr 2的中间结构域中插入环，这在人TAP-p15中不存在。值得注意的是，当Mex 67环中带正电荷的氨基酸突变时，Mex 67-Mtr 2与前60 S颗粒和5S rRNA的相互作用被抑制，并且60 S亚基而不是mRNA在细胞核中积累。因此，一般的mRNA输出Mex 67-Mtr 2含有一个独特的静电相互作用表面，用于运输60 S前核糖体货物。
The yeast Mex67-Mtr2 complex and its homologous metazoan counterpart TAP-p15 operate as nuclear export receptors by binding and translocating mRNA through the nuclear pore complexes. Here, we show how Mex67-Mtr2 can also function in the nuclear export of the ribosomal 60S subunit. Biochemical and genetic studies reveal a previously unrecognized interaction surface on the NTF2-like scaffold of the Mex67-Mtr2 heterodimer, which in vivo binds to pre-60S particles and in vitro can interact with 5S rRNA. Crucial structural requirements for this binding platform are loop insertions in the middle domain of Mex67 and Mtr2, which are absent from human TAP-p15. Notably, when the positively charged amino acids in the Mex67 loop are mutated, interaction of Mex67-Mtr2 with pre-60S particles and 5S rRNA is inhibited, and 60S subunits, but not mRNA, accumulate in the nucleus. Thus, the general mRNA exporter Mex67-Mtr2 contains a distinct electrostatic interaction surface for transporting 60S preribosomal cargo.