Conceptual and Methodological Considerations on mRNA and Proteins as Intercellular and Long-Distance Signals

High-throughput studies identified approximately one-fifth of Arabidopsis protein-encoding transcripts to be graft transmissible and to move over long distances in the phloem. In roots, one-fifth of transcription factors were annotated as non-cell autonomous, moving between cells. Is this massive transport a way of interorgan and cell-cell communication or does it serve different purposes? On the tissue level, many microRNAs (miRNAs) and all small interfering RNAs (siRNAs) act non-cell autonomously. Why are these RNAs and proteins not just expressed in cells where they exert their function? Short- and long-distance transport of these macromolecules raises the question of whether all mobile mRNAs and transcription factors could be defined as signaling molecules. Since the answer is not clear yet, we will discuss in this review conceptual approaches to this phenomenon using a single mobile signaling macromolecule, FLOWERING LOCUS T, which has been characterized extensively. We conclude that careful individual studies of mobile macromolecules are necessary to uncover their biological function and the observed massive mobility. To stimulate such studies, we provide a review summarizing the resourceful wealth of experimental approaches to this intriguing question and discuss methodological scopes and limits.