HIV-1-induced translocation of CPSF6 to biomolecular condensates.

Cleavage and polyadenylation specificity factor subunit 6 (CPSF6, also known as CFIm68) is a 68 kDa component of the mammalian cleavage factor I (CFIm) complex. CPSF6 plays a role in maturation of the 3′ untranslated regions (UTR) of pre-mRNAs modulating mRNA alternative polyadenylation (APA), which determines the length of the 3′ UTR. HIV-1 induces translocation of CPSF6 and CPSF5 from nuclear paraspeckles to speckles, which are biomolecular condensates. Since depletion of CPSF6 modestly affects the ability of HIV-1 to replicate in primary cells, we hypothesize that the translocation of CPSF6 to speckles is a viral mechanism used to affect APA, which results in the modulation of cellular expression in favor of the virus, and may have important consequences in the identification of latent viral reservoirs. HIV-1-induced translocation of CPSF6 to biomolecular condensates may induce a change in the biochemical properties of the protein. Cleavage and polyadenylation specificity factor subunit 6 (CPSF6, also known as CFIm68) is a 68 kDa component of the mammalian cleavage factor I (CFIm) complex that modulates mRNA alternative polyadenylation (APA) and determines 3′ untranslated region (UTR) length, an important gene expression control mechanism. CPSF6 directly interacts with the HIV-1 core during infection, suggesting involvement in HIV-1 replication. Here, we review the contributions of CPSF6 to every stage of the HIV-1 replication cycle. Recently, several groups described the ability of HIV-1 infection to induce CPSF6 translocation to nuclear speckles, which are biomolecular condensates. We discuss the implications for CPSF6 localization in condensates and the potential role of condensate-localized CPSF6 in the ability of HIV-1 to control the protein expression pattern of the cell. [ABSTRACT FROM AUTHOR]