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Institute for Molecular Bioscience, ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane QLD 4072, Australia

(Correspondence should be addressed to J S Mattick; Email: j.mattick{at}imb.uq.edu.au)

^* *(M E Dinger and T R Mercer contributed equally to this work)

RNA is emerging as a major component of the regulatory circuitry that underpins the development and physiology of complex organisms. Here we review recent evidence that suggests that RNA may supplement endocrine and paracrine signaling by small molecules and proteins, and act as an efficient and evolutionarily flexible source of sequence-specific information transfer between cells, both locally and systemically. As such, RNA signaling may play a central but previously hidden role in multicellular ontogeny, homeostasis, and transmitted epigenetic memory.