title: Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines.
abstract: Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency and lymphomagenesis. Using PAR-CLIP, a technology which allows the direct and transcriptome-wide identification of miRNA targets, we delineate the target sites for all viral and cellular miRNAs expressed in PEL cell lines. The resulting data set revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs, including many involved in pathways relevant to KSHV pathogenesis. Moreover, 58% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of cellular miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, this study identifies an extensive list of KSHV miRNA targets, which are likely to influence viral replication and pathogenesis.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. e-gottwein@northwestern.edu
authors.forename: Eva
authors.initials: E
authors.lastname: Gottwein
authors.forename: David L
authors.initials: DL
authors.lastname: Corcoran
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Mukherjee
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Skalsky
authors.forename: Markus
authors.initials: M
authors.lastname: Hafner
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Nusbaum
authors.forename: Priscilla
authors.initials: P
authors.lastname: Shamulailatpam
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Love
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dave
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.forename: Uwe
authors.initials: U
authors.lastname: Ohler
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Cullen
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000235:genetics* / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral
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