Editors' ChoiceIntercellular Transfer

Pass It On

Science Signaling  01 Sep 2009:
Vol. 2, Issue 86, pp. ec288
DOI: 10.1126/scisignal.286ec288

Small noncoding RNAs, such as short interfering RNAs (siRNAs) and microRNAs (miRNAs), regulate gene expression by targeting mRNAs for degradation. Mechanisms exist in plants and worms for the transfer of small RNAs from cell to cell, but similar pathways have not been characterized for mammalian cells, although small RNAs have been found in vesicles secreted from mammalian cells. Rechavi et al. investigated a cell contact–dependent mechanism for the transfer of small RNAs from human BL2 B cells to a T cell line. Flow cytometric analysis showed the transfer of fluorescently tagged miRNA-like oligonucleotides from transfected BL2 cells to the T cells in coculture. Green fluorescent protein (GFP) was not transferred from transfected BL2 cells to the T cells, suggesting that transfer of oligonucleotides from one cell to another was selective. Transfer of tagged small RNAs in the opposite direction, from transfected T cells to BL2 cells, also occurred. Separating the BL2 cells from the T cells by a semipermeable membrane almost completely blocked transfer of the tagged small RNAs. Conditions that increased the strength of interaction between the donor and acceptor cells increased the efficiency of transfer of the small RNAs. Coculture of Raji cells, a B cell line carrying the Epstein-Barr virus, with T cells resulted in the transfer of an EBV-specific miRNA, as detected by sequence analysis of the T cell fraction. Finally, short hairpin RNAs (shRNAs) were transferred from transfected B cells to T cells, and reporter assays showed that the transferred shRNAs were functional. Together, these data suggest a cell contact–dependent mechanism for the transfer of small RNAs that might regulate gene expression nonautonomously.

O. Rechavi, Y. Erlich, H. Amram, L. Flomenblit, F. V. Karginov, I. Goldstein, G. J. Hannon, Y. Kloog, Cell contact-dependent acquisition of cellular and viral nonautonomously encoded small RNAs. Genes Dev. 23, 1971–1979 (2009). [Abstract] [Full Text]