Novel roles for miRNA
Among the most fascinating properties of small interfering (siRNA) and miRNA molecules is their ability to cross cell boundaries. Although different mechanisms may be in place for facilitating this transmission, the non-cell autonomous nature of the process raises the question of how it is regulated. In answer to this, the EU-funded project 'Deciphering RNAi machineries required for miRNAs cell-to-cell transfer in mammals' (DRIMTIM) plans to test different hypotheses. DRIMTIM scientists will explore whether there are miRNA-producing and -receiving cells, and if the release of miRNA through the membrane is a polarised process. The latter is also supported by the fact that miRNA function is tightly linked to vesicles within cells. To obtain information on the cell-to-cell movement of small RNA in mammals, the consortium has utilised cancer cells and the mammary gland system as models. It had to face the challenge of monitoring miRNA concentrations at the cellular level. For this purpose, they generated an innovative, sensitive and specific miRNA sensor strategy based on the fluorescent detection of miR21 in a transgenic cancer cell line. This cell line has no endogenous miR21 so it can serve as a sensor for the cell-to-cell movement of miR21. In addition, researchers identified differences in RNA silencing complexes, which reinforce the differential capacity of cells to either emit or receive small RNAs. This could be a result of qualitative and quantitative differences in various factors implicated in the processing and secretion of miRNAs. Finally, the DRIMTIM consortium investigated the physiological relevance of miRNA transfer. They found that mammalian milk contains abundant miRNAs and RNA silencing factors, and hypothesised that they serve as paracrine molecules, or as a long-distance communication system between mother and child. Experiments in mice demonstrated that miRNAs secreted in the milk are indeed transferred to the pups. Further investigation is, however, required to unequivocally demonstrate the function of these molecules.
Keywords
miRNAs, small RNA molecules, cell-to-cell transfer, mammal
