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Genes & Dev. 23 (16): 1971-1979

Copyright © 2009 by Cold Spring Harbor Laboratory Press.

Cell contact-dependent acquisition of cellular and viral nonautonomously encoded small RNAs

Oded Rechavi1,4, Yaniv Erlich2,4, Hila Amram3,4, Lena Flomenblit3, Fedor V. Karginov2, Itamar Goldstein3, Gregory J. Hannon2,5,, and Yoel Kloog1,6

1 Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv, Israel;
2 Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
3 Immunology Program, Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel

Abstract: In some organisms, small RNA pathways can act nonautonomously, with responses spreading from cell to cell. Dedicated intercellular RNA delivery pathways have not yet been characterized in mammals, although secretory compartments have been found to contain RNA. Here we show that, upon cell contact, T cells acquire from B cells small RNAs that can impact the expression of target genes in the recipient T cells. Synthetic microRNA (miRNA) mimetics, viral miRNAs expressed by infected B cells, and endogenous miRNAs could all be transferred into T cells. These mechanisms may allow small RNA-mediated communication between immune cells. The documented transfer of viral miRNAs raises the possible exploitation of these pathways for viral manipulation of the host immune response.

Key Words: microRNA • shRNA • intercellular transfer • immunity

Received for publication February 7, 2009. Accepted for publication July 2, 2009.

4 These authors contributed equally to this work.

5 Corresponding authors.

E-MAIL hannon{at}; FAX (516) 367-8874.

6 E-MAIL kloog{at}; FAX 972-3-6407643.

Article is online at

Supplemental material is available at

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