title: Depletion of hnRNP A2/B1 overrides the nuclear retention of the HIV-1 genomic RNA.
abstract: hnRNP A2 is a cellular protein that is important for nucleocytoplasmic and cytosolic trafficking of the HIV-1 genomic RNA. Both hnRNP A2's interaction with HIV-1 RNA and its expression levels influence the activities of Rev in mediating nucleocytoplasmic export of the HIV-1 genomic RNA. While the lack of Rev expression during HIV-1 gene expression results in nuclear retention of HIV-1 genomic RNA, we show here by fluorescence in situ hybridization and fractionation studies that the genomic RNA translocates to the cytoplasm when hnRNP A2/B1 are depleted from cells. Polyribosome analyses revealed that the genomic RNA was shunted into a cytoplasmic, dense polyribosomal fraction. This fraction contained several RNA-binding proteins involved in viral gene expression and RNA trafficking but did not contain the translation initiation factor, eIF4G1. Amino acid incorporation into nascent polypeptides in this fraction was also greatly reduced, demonstrating that this fraction contains mRNAs that are poorly translated. These results demonstrate that hnRNP A2/B1 expression plays roles in the nuclear retention of the HIV-1 genomic RNA in the absence of Rev and in the release of the genomic RNA from translationally inactive, cytoplasmic RNP complexes.
authors.affiliation: HIV-1 RNA Trafficking Laboratory; Lady Davis Institute at the Jewish General Hospital; Montréal, Québec, Canada; Department of Microbiology & Immunology; McGill University; Montréal, Québec, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordon
authors.affiliation: HIV-1 RNA Trafficking Laboratory; Lady Davis Institute at the Jewish General Hospital; Montréal, Québec, Canada; Department of Medicine; Division of Experimental Medicine; McGill University; Montréal, Québec, Canada.
authors.forename: Lara
authors.initials: L
authors.lastname: Ajamian
authors.affiliation: HIV-1 RNA Trafficking Laboratory; Lady Davis Institute at the Jewish General Hospital; Montréal, Québec, Canada; Department of Medicine; Division of Experimental Medicine; McGill University; Montréal, Québec, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Valiente-Echeverrìa
authors.affiliation: HIV-1 RNA Trafficking Laboratory; Lady Davis Institute at the Jewish General Hospital; Montréal, Québec, Canada; Department of Medicine; Division of Experimental Medicine; McGill University; Montréal, Québec, Canada.
authors.forename: Kathy
authors.initials: K
authors.lastname: Lévesque
authors.affiliation: Dartmouth Medical School; Department of Medicine; Lebanon, NH, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Rigby
authors.affiliation: HIV-1 RNA Trafficking Laboratory; Lady Davis Institute at the Jewish General Hospital; Montréal, Québec, Canada; Department of Microbiology & Immunology; McGill University; Montréal, Québec, Canada; Department of Medicine; Division of Experimental Medicine; McGill University; Montréal, Québec, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
mesh_terms: D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D034443:RNA Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012333:RNA, Messenger; D012367:RNA, Viral; C439768:hnRNP A2; D054321:rev Gene Products, Human Immunodeficiency Virus
keywords: HIV-1 RNA; RNA trafficking; hnRNP A2/B1; nuclear retention