TY - JOUR
T1 - Viral microRNA targetome of KSHV-Infected primary effusion lymphoma cell lines
AU - Gottwein, Eva
AU - Corcoran, David L.
AU - Mukherjee, Neelanjan
AU - Skalsky, Rebecca L.
AU - Hafner, Markus
AU - Nusbaum, Jeffrey D.
AU - Shamulailatpam, Priscilla
AU - Love, Cassandra L.
AU - Dave, Sandeep S.
AU - Tuschl, Thomas
AU - Ohler, Uwe
AU - Cullen, Bryan R.
N1 - Funding Information:
The authors would like to thank Dr. Dirk Dittmer for cell lines, John Whitesides in the Duke Center for AIDS Research BSL3 Flow Cytometry Core Facility for flow cytometry, and Eleonora Forte for comments on the manuscript. Microarrays were performed in the Duke Microarray Facility. Sequencing was performed by the Duke Genome Sequencing and Analysis Core Facility. This research was supported by National Institutes of Health (NIH) K99-CA-137860-01A1/R00-CA-137860-02 (to E.G.) and by NIH R01-AI067968 (to B.R.C.). R.L.S. was supported by NIH T32-CA009111. M.H. is supported by a fellowship of the Charles Revson, Jr. Foundation. T.T. is a Howard Hughes Medical Institute (HHMI) investigator, and work in his laboratory was supported by NIH grants GM073047 and MH08442, NIH Challenge Grant RC1CA145442, and the Starr Foundation.
PY - 2011/11/17
Y1 - 2011/11/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2011.09.012
DO - 10.1016/j.chom.2011.09.012
M3 - Article
C2 - 22100165
AN - SCOPUS:81755161195
SN - 1931-3128
VL - 10
SP - 515
EP - 526
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -