title: N-Myristoyltransferase 1 enhances human immunodeficiency virus replication through regulation of viral RNA expression level.
abstract: N-myristoyltransferase (NMT) catalyzes protein N-myristoylation. It has been suggested that the isozyme NMT1 enhances the replication of human immunodeficiency virus type-1 (HIV-1). However, the details of the mechanism by which NMT1 does so remain unclear. In this study, we investigated NMT1-binding proteins by co-immunoprecipitation and mass spectrometry. As a result, several RNA-binding proteins including ribosomal proteins, NMT isozymes, and hnRNP A2/B1 were observed to bind to NMT1, as mediated mainly by RNA. Interestingly, only hRNP A2/B1 was found to associate with NMT1 without mediation by RNA. It was also suggested that hnRNP A2/B1 contributes to the formation of complexes of high molecular weights involving NMT1. Knockdown of hnRNP A2/B1 resulted in the enhancement of viral replication with an increase in the expression level of viral RNA in HIV-1-producing cells. On the other hand, knockdown of NMT1 resulted in the attenuation of viral replication with the decrease in the expression level of viral RNA in HIV-1-producing cells. Additionally, overexpression of NMT1 induced the enhancement of viral replication with the increase in the expression level of the viral RNA. These findings suggest that both NMT1 and hnRNP A2/B1 take part in the regulation of HIV-1 RNA expression through their mutual opposite effects on the viral RNA expression in HIV-1-producing cells.
authors.affiliation: Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-Ku, Kumamoto 8620973, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Innovative Collaboration Organization, Kumamoto University, 2-39-1 Kurokami, Chuo-Ku, Kumamoto 8608555, Japan; Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-Ku, Kumamoto 8620973, Japan. Electronic address: tkmnnbtk@gpo.kumamoto-u.ac.jp.
authors.forename: Nobutoki
authors.initials: N
authors.lastname: Takamune
authors.affiliation: Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-Ku, Kumamoto 8620973, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kishimoto
authors.affiliation: Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-Ku, Kumamoto 8620973, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
authors.affiliation: Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-Ku, Kumamoto 8620973, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
mesh_terms: D000217:Acyltransferases / Q000378:metabolism / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D012367:RNA, Viral / Q000235:genetics*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012367:RNA, Viral; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase
keywords: HIV-1; HnRNP A2/B1; N-myristoyltransferase 1; RNA