Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 328 (5985): 1563-1566

Copyright © 2010 by the American Association for the Advancement of Science

Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA

Demián Cazalla, Therese Yario, Joan A. Steitz*

Abstract: T cells transformed by Herpesvirus saimiri express seven viral U-rich noncoding RNAs of unknown function called HSURs. We noted that conserved sequences in HSURs 1 and 2 constitute potential binding sites for three host-cell microRNAs (miRNAs). Coimmunoprecipitation experiments confirmed that HSURs 1 and 2 interact with the predicted miRNAs in virally transformed T cells. The abundance of one of these miRNAs, miR-27, is dramatically lowered in transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR 1 demonstrate that it directs degradation of mature miR-27 in a sequence-specific and binding-dependent manner. This viral strategy illustrates use of a ncRNA to manipulate host-cell gene expression via the miRNA pathway.

Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.

* To whom correspondence should be addressed. E-mail: joan.steitz{at}

Pervasive Transcription of a Herpesvirus Genome Generates Functionally Important RNAs.
S. P. Canny, T. A. Reese, L. S. Johnson, X. Zhang, A. Kambal, E. Duan, C. Y. Liu, and H. W. Virgin (2014)
mBio 5, e01033-13
   Abstract »    Full Text »    PDF »
The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122.
A. P. E. Roberts, R. Doidge, A. W. Tarr, and C. L. Jopling (2014)
Nucleic Acids Res. 42, 1257-1269
   Abstract »    Full Text »    PDF »
Emerging Roles of Competing Endogenous RNAs in Cancer: Insights from the Regulation of PTEN.
A. de Giorgio, J. Krell, V. Harding, J. Stebbing, and L. Castellano (2013)
Mol. Cell. Biol. 33, 3976-3982
   Abstract »    Full Text »    PDF »
ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry.
F. A. Karreth and P. P. Pandolfi (2013)
Cancer Discovery 3, 1113-1121
   Abstract »    Full Text »    PDF »
Hepatitis B Viral RNA Directly Mediates Down-regulation of the Tumor Suppressor MicroRNA miR-15a/miR-16-1 in Hepatocytes.
Y. Wang, L. Jiang, X. Ji, B. Yang, Y. Zhang, and X.-D. Fu (2013)
J. Biol. Chem. 288, 18484-18493
   Abstract »    Full Text »    PDF »
LncRNA loc285194 is a p53-regulated tumor suppressor.
Q. Liu, J. Huang, N. Zhou, Z. Zhang, A. Zhang, Z. Lu, F. Wu, and Y.-Y. Mo (2013)
Nucleic Acids Res. 41, 4976-4987
   Abstract »    Full Text »    PDF »
MicroRNA-27a Regulates Lipid Metabolism and Inhibits Hepatitis C Virus Replication in Human Hepatoma Cells.
T. Shirasaki, M. Honda, T. Shimakami, R. Horii, T. Yamashita, Y. Sakai, A. Sakai, H. Okada, R. Watanabe, S. Murakami, et al. (2013)
J. Virol. 87, 5270-5286
   Abstract »    Full Text »    PDF »
Non-coding RNAs in homeostasis, disease and stress responses: an evolutionary perspective.
P. P. Amaral, M. E. Dinger, and J. S. Mattick (2013)
Briefings in Functional Genomics 12, 254-278
   Abstract »    Full Text »    PDF »
In-Depth Analysis of the Interaction of HIV-1 with Cellular microRNA Biogenesis and Effector Mechanisms.
A. W. Whisnant, H. P. Bogerd, O. Flores, P. Ho, J. G. Powers, N. Sharova, M. Stevenson, C.-H. Chen, and B. R. Cullen (2013)
mBio 4, e00193-13
   Abstract »    Full Text »    PDF »
RNase III-independent microRNA biogenesis in mammalian cells.
T. Maurin, D. Cazalla, J.-S. Yang, D. Bortolamiol-Becet, and E. C. Lai (2012)
RNA 18, 2166-2173
   Abstract »    Full Text »    PDF »
Ultrashort and progressive 4sU-tagging reveals key characteristics of RNA processing at nucleotide resolution.
L. Windhager, T. Bonfert, K. Burger, Z. Ruzsics, S. Krebs, S. Kaufmann, G. Malterer, A. L'Hernault, M. Schilhabel, S. Schreiber, et al. (2012)
Genome Res. 22, 2031-2042
   Abstract »    Full Text »    PDF »
Pseudogenes: Newly Discovered Players in Human Cancer.
L. Poliseno (2012)
Science Signaling 5, re5
   Abstract »    Full Text »    PDF »
miRcode: a map of putative microRNA target sites in the long non-coding transcriptome.
A. Jeggari, D. S. Marks, and E. Larsson (2012)
Bioinformatics 28, 2062-2063
   Abstract »    Full Text »    PDF »
Murine cytomegalovirus infection of cultured mouse cells induces expression of miR-7a.
A. Dittmer and K. Forstemann (2012)
J. Gen. Virol. 93, 1537-1547
   Abstract »    Full Text »    PDF »
Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes.
C. Villota, A. Campos, S. Vidaurre, L. Oliveira-Cruz, E. Boccardo, V. A. Burzio, M. Varas, J. Villegas, L. L. Villa, P. D. T. Valenzuela, et al. (2012)
J. Biol. Chem. 287, 21303-21315
   Abstract »    Full Text »    PDF »
Temporal- and Strain-Specific Host MicroRNA Molecular Signatures Associated with Swine-Origin H1N1 and Avian-Origin H7N7 Influenza A Virus Infection.
E.-K. Loveday, V. Svinti, S. Diederich, J. Pasick, and F. Jean (2012)
J. Virol. 86, 6109-6122
   Abstract »    Full Text »    PDF »
West Nile Virus Noncoding Subgenomic RNA Contributes to Viral Evasion of the Type I Interferon-Mediated Antiviral Response.
A. Schuessler, A. Funk, H. M. Lazear, D. A. Cooper, S. Torres, S. Daffis, B. K. Jha, Y. Kumagai, O. Takeuchi, P. Hertzog, et al. (2012)
J. Virol. 86, 5708-5718
   Abstract »    Full Text »    PDF »
Regulation of Cyclin T1 and HIV-1 Replication by MicroRNAs in Resting CD4+ T Lymphocytes.
K. Chiang, T.-L. Sung, and A. P. Rice (2012)
J. Virol. 86, 3244-3252
   Abstract »    Full Text »    PDF »
Effective Small RNA Destruction by the Expression of a Short Tandem Target Mimic in Arabidopsis.
J. Yan, Y. Gu, X. Jia, W. Kang, S. Pan, X. Tang, X. Chen, and G. Tang (2012)
PLANT CELL 24, 415-427
   Abstract »    Full Text »    PDF »
Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target.
V. Libri, A. Helwak, P. Miesen, D. Santhakumar, J. G. Borger, G. Kudla, F. Grey, D. Tollervey, and A. H. Buck (2012)
PNAS 109, 279-284
   Abstract »    Full Text »    PDF »
Viruses and microRNAs: RISCy interactions with serious consequences.
B. R. Cullen (2011)
Genes & Dev. 25, 1881-1894
   Abstract »    Full Text »    PDF »
Down-Regulation of a Host microRNA by a Viral Noncoding RNA.
D. Cazalla and J. A. Steitz (2010)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Paring MiRNAs Through Pairing.
A. E. Pasquinelli (2010)
Science 328, 1494-1495
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882