From genomics to post-genomics: back to the origins?

The purpose of this review is to emphasize the multiplicity and importance, physiological and pathological, of gene regulation levels which operate after the initiation step of transcription. Albeit crucial, this step is only the first one of a long cascade of events which eventually end up in the selection of functional messengers appropriate to the nature of the cells and to their immediate needs. Throughout this long pathway, of which only a few steps will be mentioned here, this review will attempt to address the central role played by RNA, not only as a substrate but as an actor of its own regulation. Emphasis will be put on the numerous connections with pathology up to the development of new therapeutics specifically targeting RNA. It highlights the perennity of basic questions, nearly half a century old, for which genomics, short of new concepts, will provide the databases and tools required to access to the immense field of functional genomics, the only one likely to bring relevant answers for therapeutics.