title: RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1.
abstract: The 5' untranslated region (UTR) of retroviruses contain structured replication motifs that impose barriers to efficient ribosome scanning. Two RNA structural motifs that facilitate efficient translation initiation despite a complex 5' UTR are internal ribosome entry site (IRES) and 5' proximal post-transcriptional control element (PCE). Here, stringent RNA and protein analyses determined the 5' UTR of spleen necrosis virus (SNV), reticuloendotheliosis virus A (REV-A) and human T-cell leukemia virus type 1 (HTLV-1) exhibit PCE activity, but not IRES activity. Assessment of SNV translation initiation in the natural context of the provirus determined that SNV is reliant on a cap-dependent initiation mechanism. Experiments with siRNAs identified that REV-A and HTLV-1 PCE modulate post-transcriptional gene expression through interaction with host RNA helicase A (RHA). Analysis of hybrid SNV/HTLV-1 proviruses determined SNV PCE facilitates Rex/Rex responsive element-independent Gag production and interaction with RHA is necessary. Ribosomal profile analyses determined that RHA is necessary for polysome association of HTLV-1 gag and provide direct evidence that RHA is necessary for efficient HTLV-1 replication. We conclude that PCE/RHA is an important translation regulatory axis of multiple lymphotropic retroviruses. We speculate divergent retroviruses have evolved a convergent RNA-protein interaction to modulate translation of their highly structured mRNA.
authors.affiliation: Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210-1093, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Bolinger
authors.forename: Alper
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Tiffiney Roberts
authors.initials: TR
authors.lastname: Hartman
authors.forename: Melinda Butsch
authors.initials: MB
authors.lastname: Kovacic
authors.forename: Soledad
authors.initials: S
authors.lastname: Fernandez
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ye
authors.forename: Mary
authors.initials: M
authors.lastname: Forget
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Green
authors.forename: Kathleen
authors.initials: K
authors.lastname: Boris-Lawrie
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry*; D017986:Reticuloendotheliosis Viruses, Avian / Q000235:genetics*; D020079:Terminal Repeat Sequences; D053079:Trager duck spleen necrosis virus / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D015683:Gene Products, gag; D012367:RNA, Viral; D020365:RNA Helicases