title: Kaposi's sarcoma-associated herpesvirus encodes a mimic of cellular miR-23.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) expresses ∼20 viral microRNAs (miRNAs) in latently infected cells. We have previously shown that two of these miRNAs function as mimics of the cellular miRNAs miR-155 and miR-142-3p. Two additional KSHV miRNAs, miR-K3+1 and miR-K3, share perfect and offset 5' homology with cellular miR-23, respectively. Here, we report a single nucleotide polymorphism that causes miR-K3+1 expression in a subset of KSHV-infected primary effusion lymphoma cell lines as a consequence of altered processing of the primary transcript by the Microprocessor complex. We confirm that miR-K3+1 regulates miR-23 targets, which is expected because these miRNAs share the entire seed region (nucleotides 2 to 8). Surprisingly, we found that miR-K3 also regulates miR-23 targets, despite offset seed sequences. In addition, the offset homology of miR-K3 to miR-23 likely allows this viral miRNA to expand its target repertoire beyond the targets of miR-23. Because miR-23 is highly expressed in endothelial cells but expressed at only low levels in B cells, we hypothesize that miR-K3 may function to introduce miR-23-like activities into KSHV-infected B cells. Together, our data demonstrate that KSHV has evolved at least three distinct viral miRNAs to tap into evolutionarily conserved cellular miRNA-regulatory networks. Furthermore, our data allow fundamental insights into the generation and functional impact of miRNA 5' end variation.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Manzano
authors.forename: Priscilla
authors.initials: P
authors.lastname: Shamulailatpam
authors.forename: Archana N
authors.initials: AN
authors.lastname: Raja
authors.forename: Eva
authors.initials: E
authors.lastname: Gottwein
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D017735:Virus Latency
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral