The nuclear export of mRNA is a multistep process mediated by mRNA-export protein complexes (mRNP). The formation of these complexes takes place concurrently and in coordination with the steps involved in mRNA formation, starting from the synthesis of nascent pre-mRNA molecule, through its splicing and subsequent processing steps. One such step is the recruitment of export factors, directly or via other mediators, onto the mRNA molecule during or after transcription. A second critical step is the targetting of the mRNP complex to the nuclear pore, which is composed of large multi-protein structures called the nuclear pore complex (NPC). Following targeting, the translocation of the mRNP complexes is thought to occur through the NPC by repeated interaction between mRNPs and the hydrophobic phenylalanine glycine (-FG) patches on the pore associated proteins lining the wall of the tubular pore channel. At the cytoplamic side the mRNPs are released. Our studies where designed to define these different steps of mRNA export, and identify the protein-protein interaction that is required for progression of the mRNP-complexes through various steps of the mRNA export proves.The breast cancer tumor suppressor BRCA-2 interacting protein, DSS1, and its homolog are critical for DNA recombination in eukaryotic cells. We found that Dss1p, along with Mlo3p and Uap56p, Schizosaccharmyces pombe (S. pombe) homologs of two mRNAs export factorsa of the NXF-NXT pathway, is required for mRNA export in S. pombe. Previously we showed that the nuclear pore-associated Rae1p is an essential mRNA export factor in S. pombe. We have shown that Dss1p and Uap56p function by linking mRNA export adaptor Mlo3p to Rae1p for targeting mRNA-protein (mRNP) complex to the proteins of the nuclear pore complex. Dss1p preferentially recruits to genes in vivo and interacts with -FG (phenylalanine glycine) nucleoporins in vivo and in vitro. Thus, Dss1p may function at multiple steps of mRNA export, from mRNP biogenesis to targeting and translocation through the NPC.
| Thakurta, Anjan G; Gopal, Ganesh; Yoon, Jin Ho et al. (2004) Conserved nuclear export sequences in Schizosaccharomyces pombe Mex67 and human TAP function in mRNA export by direct nuclear pore interactions. J Biol Chem 279:17434-42 |
