Abstract
Cellular mRNAs are exported from the nucleus as fully spliced RNAs. Proofreading mechanisms eliminateunprocessed and irregular pre-mRNAs to control the quality of gene expression. Retroviruses need toexport partially spliced and unspliced full-length RNAs to the cytoplasm where they serve as templatesfor protein synthesis and/or as encapsidated RNA in progeny viruses. Genetically complex retrovirusessuch as HIV-1 use Rev-equivalent proteins to export intron-retaining RNA from the nucleus using thecellular CRM1-driven nuclear export machinery. By contrast, genetically simpler retroviruses such asmurine leukaemia virus (MLV) recruit the NXF1 RNA export machinery. In this study, we reveal for thefirst time that MLV hijacks both NXF1 and CRM1-dependent pathways to achieve optimal replicationcapacity. The CRM1-pathway marks the MLV full-length RNA (FL RNA) for packaging, while NXF1-drivennuclear export is coupled to translation. Thus, the cytoplasmic function of the viral RNA is determinedearly in the nucleus. Depending on the nature of ribonucleoprotein complex formed on FL RNA cargo inthe nucleus, the FL RNA will be addressed to the translation machinery sites or to the virus-assemblysites at the plasma membrane.