Rae1-mediated nuclear export of Rnc1 is an important determinant in controlling MAPK signaling

Abstract

In eukaryotic cells, RNA binding proteins (RBPs) play critical roles in regulating almost every aspect of gene expression, often shuttling between the nucleus and the cytoplasm. They are also key determinants in cell fate via controlling the target mRNAs under the regulation of various signaling pathways in response to environmental stresses. Therefore, understanding the mechanisms that couple the location of mRNA and RBPs is a major challenge in the field of gene expression and signal responses. In fission yeast, a KH-type RBP Rnc1 negatively regulates MAPK signaling activation via mRNA stabilization of the dual-specificity MAPK phosphatase Pmp1, which dephosphorylates MAPK Pmk1. Rnc1 also serves as a target of MAPK phosphorylation, which makes a feedback loop mediated by an RBP. We recently discovered that the nuclear export of Rnc1 requires mRNA-binding ability and the mRNA export factor Rae1. This strongly suggested the presence of an mRNA-export system, which recognizes the mRNA/RBP complex and dictates the location and post-transcriptional regulation of mRNA cargo. Here, we briefly review the known mechanisms of general nuclear transporting systems, with an emphasis on our recent findings on the spatial regulation of Rnc1 and its impact on the regulation of the MAPK signal transduction cascade.

The architecture of lipid droplets in the diatom Phaeodactylum tricornutum

“…Since aminoacids are nitrogen-rich molecules, protein synthesis is not expected in a nitrogen starved context [121,132,133], so the presence of this equipment could find a rational, either for the translation of a specific subset of mRNA, or in preparation of a massive production of proteins when the cells are not stressed any more. In line with this hypothesis, the RAE1 (Ribonucleic Acid Export 1) component of nuclear pore complex, involved in mRNA export [134], was not immunodetected in whole cell extracts after cultivation in the absence of nitrogen ( Figure 5). We can therefore suppose that the recovery of cells relies on mRNAs stored in the cytosol during starvation.…”

The Putative RNA-Binding Protein Dri1 Promotes the Loading of Kinesin-14/Klp2 to the Mitotic Spindle and Is Sequestered into Heat-Induced Protein Aggregates in Fission Yeast

“…A subset of RBPs, particularly those binding mRNA, is exported from the nucleus and locates to the cytoplasm by a transport factor Rae1 [ 49 , 50 , 51 ]. Accordingly, rae1-167 ts mutants exhibit defective mRNA export and rapidly accumulate poly(A) + RNA and mRNA-binding proteins in the nucleus at the restrictive temperature [ 49 , 52 , 53 ]. Given this notion and the existence of RNA-binding motifs within Dri1, we investigated the subcellular localization of Dri1-GFP in the rae1-167 mutant cells.…”

Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer

“…Furthermore, we provide clinical and biological evidence that the mitotic checkpoint regulator RAE1 could be a therapeutic target to overcome therapeutic resistance of CRC. Recently, as a component of the nuclear pore complex, RAE1 has been reported to control MAPK signaling 45 and to interact with ORF6 in SARS‐COV‐2/COVID‐19. 46 , 47 As a component of the nuclear pore complex, RAE1 may play several important roles in mRNA export and signaling activation, not only in cancer cells but also in normal cells and viruses.…”