The nucleo-cytoplasmic export of mRNAs is a highly coordinated process which is tightly coupled to transcription, RNA-processing and -packaging to an export competent messenger ribonucleoprotein-particle (mRNP). This evolutionarily highly conserved process requires two large complexes, the TRanscription and EXport complex 1 and 2 (TREX-1 and TREX-2) for the proper packaging of the mRNAs and for the recruitment of the mRNA export receptor Mex67/Mtr2 (TAP/p15) to allow the translocation of the mRNPs through the nuclear pore complexes (NPC) into the cytoplasm. While TREX-1 complex is located in the nucleus, the TREX-2 complex was found to be localized at the nuclear periphery, due to its stable interaction with the NPC.

Here we identified and characterized a novel, mobile form of the TREX-2 complex (mTREX-2) in the fission yeast Schizosaccharomyces pombe, which consists of a Sac3 homologue protein Nsc3 and the TREX-2 members Pci2 (S.c. Thp1), Dss1 (S.c. Sem1). Sequence analyses revealed that Nsc3 is evolutionarily conserved up to humans and it shares homology with the more highly conserved N-terminal half of the TREX-2 scaffold protein Sac3, while the NPC interacting C-terminal part of Sac3 is missing. As a consequence, unlike Sac3, Nsc3 is not anchored to the NPC, and it is distributed in the nuclear interior. Loss of Nsc3 leads to mRNA export defects which synergistically increase when combined with a mex67 mutant indicating that Nsc3 plays an important role in the Mex67 mediated mRNA export process. Genome-wide chromatin and RNA co-immunoprecipitation analyses show that the mTREX-2 complex is co-transcriptionally recruited to actively transcribed genes. Nsc3 binds over the entire length of the transcribed genes with a slight increase towards the 3’ end as has been shown for the export receptor Mex67. Interestingly, the mTREX-2 complex binds to the same mRNAs as the TREX-2 complex although these complexes do not show any physical contact in vivo and therefore rather seem to co-exist as independent complexes. Further studies will be required to understand if the TREX-2 complex and its nucleoplasmatic variant act in alternative mRNP biogenesis and export pathways or if they rather complement each other and act at spatiotemporally separate steps to promote a tightly controlled mRNP biogenesis and export process to the cytoplasm.