title: Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression.
abstract: Control of RNA processing plays a major role in HIV-1 gene expression. To explore the role of several hnRNP proteins in this process, we carried out a siRNA screen to examine the effect of depletion of hnRNPs A1, A2, D, H, I and K on HIV-1 gene expression. While loss of hnRNPs H, I or K had little effect, depletion of A1 and A2 increased expression of viral structural proteins. In contrast, reduced hnRNP D expression decreased synthesis of HIV-1 Gag and Env. Loss of hnRNP D induced no changes in viral RNA abundance but reduced the accumulation of HIV-1 unspliced and singly spliced RNAs in the cytoplasm. Subsequent analyses determined that hnRNP D underwent relocalization to the cytoplasm upon HIV-1 infection and was associated with Gag protein. Screening of the four isoforms of hnRNP D determined that, upon overexpression, they had differential effects on HIV-1 Gag expression, p45 and p42 isoforms increased viral Gag synthesis while p40 and p37 suppressed it. The differential effect of hnRNP D isoforms on HIV-1 expression suggests that their relative abundance could contribute to the permissiveness of cell types to replicate the virus, a hypothesis subsequently confirmed by selective depletion of p45 and p42.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A8, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lund
authors.forename: Miroslav P
authors.initials: MP
authors.lastname: Milev
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.forename: Tharmila
authors.initials: T
authors.lastname: Sanmuganantham
authors.forename: Kathryn
authors.initials: K
authors.lastname: Woolaway
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Sherif
authors.initials: S
authors.lastname: Abou Elela
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
authors.forename: Alan
authors.initials: A
authors.lastname: Cochrane
mesh_terms: D015870:Gene Expression; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012367:RNA, Viral / Q000032:analysis; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D020033:Protein Isoforms; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus