An elevated level of the mRNA exporter Mex67-Mtr2 in nuclear mRNPs impairs nuclear mRNA export

In eukaryotes, a crucial step in gene expression is the export of the mRNA out of nucleus. The conserved mRNA exporter Mex67-Mtr2 (NXF1-NXT1 in human) is a key factor in this process. In S. cerevisiae, it is recruited to the mRNA by the four export adaptors Hpr1, Nab2, Yra1 and Npl3 that play important yet poorly defined roles in nuclear mRNA export. Here, we show that an excess of Mex67 in nuclear mRNPs impairs nuclear mRNA export.{Delta} hpr1 cells have increased Nab2, Yra1 and Mex67 levels in nuclear mRNPs in addition to the export defect. Notably, overexpression of Nab2 or Yra1 in{Delta} hpr1 cells suppresses this export defect and reduces the Mex67 level in nuclear mRNPs to a WT level. Importantly, the increase in the Mex67 level in{Delta} hpr1 cells is not a consequence and thus the cause of the nuclear mRNA export defect. Therefore, precise regulation of the Mex67-Mtr2 level in nuclear mRNPs is essential for efficient nuclear mRNA export.