Control of gene expression by Ott1/RBM15 protein

The conserved mRNA nuclear export receptor NXF1 (Mex67 in yeast) assembles with messenger ribonucleoproteins (mRNP) in the nucleus and guides them through the nuclear pore complex (NPC) into the cytoplasm. The DEAD-box RNA helicase Dbp5 is essential for nuclear export of mRNA and is thought to dissociate Mex67 from mRNP upon translocation, thereby generating directional passage. However, the molecular mechanism by which Dbp5 recognizes Mex67-containing mRNP is not clear. Here we report that the human NXF1-binding protein RBM15 binds to DBP5 specifically and enables its direct contact with mRNA. We found that RBM15 is enriched at the nuclear envelope and colocalizes with DBP5 at the NPC. Knockout of RBM15’s orthologue in mouse (Ott1) leads to global changes in mRNA expression and excessive mRNA accumulation in the cytoplasm, indicating an essential role of RBM15 in mRNA export regulation. We propose that RBM15 acts locally at the NPC, by transiently bridging the NXF1-mRNP complexes to DBP5, thereby contributing to the substrate specificity of mRNA export. Mice harboring a low expression Ott1 allele were mated and embryos at day E11.5 were dissected and genotyped. Total RNA was isolated from whole embryos and subject to microarray analysis. The study included biological replicates of all genotypes: wt, n=2, embryos##11, 13; heterozygous, n=3, embryos##3, 10, 15 and homozygous, n=3, embryos##2, 7, 16.