Intercellular mRNA Transfer Through Tunneling Nanotubes In Mammalian Cells

RNA transfer between mammalian cells was discovered in 1972, but the mechanism for mRNA transfer was not investigated until recently. Contrary to the diffusion model suggested for small RNAs, we recently published that full-length mRNA molecules transfer from donor to acceptor cells via tunneling nanotubes (a.k.a membrane nanotubes) - actin-based long and thin cellular protrusions that are distinct from filopodia.

We used single molecule fluorescent in situ hybridization (smFISH) to show that mRNAs such as those encoding β-actin, HER2, Cyclin D1, BRCA1 and GFP are transferred in cultures of mouse embryonic fibroblasts, human cell lines and mouse/human co-cultures. We found that the transfer of either endogenous or tagged mRNAs occurs in both immortalized and primary cells, and that it is modulated by stress conditions and specific inhibitors. The mechanism and the biological significance of intercellular transfer of mRNA are currently under investigation in our lab.

Here, I will describe several of our approaches to study the scope, the mechanism and the physiological significance of mRNA transfer. I will discuss the technical difficulties we encounter and present preliminary results that provide clues about the mechanism and function.