HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3

Human immunodeficiency virus gene expression and replication are regulated at several levels. Incompletely spliced viral RNAs and full-length genomic RNA contain the RRE element and are bound by the viral trans-acting protein Rev to be transported out of the nucleus. Previously we found that the nuclear matrix protein MATR3 was a cofactor of Rev-mediated RNA export. Here we show that the pleiotropic protein PSF binds viral RNA and is associated with MATR3. PSF is involved in the maintenance of a pool of RNA available for Rev activity. However, while Rev and PSF bind the viral pre-mRNA at the site of viral transcription, MATR3 interacts at a subsequent step. We propose that PSF and MATR3 define a novel pathway for RRE-containing HIV-1 RNAs that is hijacked by the viral Rev protein.

► HIV-1 Rev activity on viral RNAs depends on host factors.
► PSF and MATR3 are cellular host factors that bind viral RNA and promote Rev activity.
► PSF and Rev associate with nascent RNA that is released to MATR3.
► PSF commits viral RRE containing RNAs to Rev mediated export through MATR3.