title: The RNA Binding Specificity of Human APOBEC3 Proteins Resembles That of HIV-1 Nucleocapsid.
abstract: The APOBEC3 (A3) cytidine deaminases are antiretroviral proteins, whose targets include human immunodeficiency virus type-1 (HIV-1). Their incorporation into viral particles is critical for antiviral activity and is driven by interactions with the RNA molecules that are packaged into virions. However, it is unclear whether A3 proteins preferentially target RNA molecules that are destined to be packaged and if so, how. Using cross-linking immunoprecipitation sequencing (CLIP-seq), we determined the RNA binding preferences of the A3F, A3G and A3H proteins. We found that A3 proteins bind preferentially to RNA segments with particular properties, both in cells and in virions. Specifically, A3 proteins target RNA sequences that are G-rich and/or A-rich and are not scanned by ribosomes during translation. Comparative analyses of HIV-1 Gag, nucleocapsid (NC) and A3 RNA binding to HIV-1 RNA in cells and virions revealed the striking finding that A3 proteins partially mimic the RNA binding specificity of the HIV-1 NC protein. These findings suggest a model for A3 incorporation into HIV-1 virions in which an NC-like RNA binding specificity is determined by nucleotide composition rather than sequence. This model reconciles the promiscuity of A3 RNA binding that has been observed in previous studies with a presumed advantage that would accompany selective binding to RNAs that are destined to be packaged into virions.
authors.affiliation: Laboratory of Retrovirology, The Rockefeller University, New York, New York, United States of America.|Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, United States of America.
authors.forename: Ashley
authors.initials: A
authors.lastname: York
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, United States of America.
authors.forename: Sebla B
authors.initials: SB
authors.lastname: Kutluay
authors.affiliation: Department of Physics, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors.forename: Manel
authors.initials: M
authors.lastname: Errando
authors.affiliation: Laboratory of Retrovirology, The Rockefeller University, New York, New York, United States of America.|Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, United States of America.|Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, New York, New York, United States of America.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000071478:APOBEC Deaminases; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase