Accumulating evidence indicates that RNA metabolism components assemble into supramolecular cellular structures to mediate functional compartmentalization within the cytoplasmic membrane of the bacterial cell. This cellular compartmentalization could play important roles in the processes of RNA degradation and maturation. These components include Hfq, an RNA chaperone protein, which is involved in the post-transcriptional control of protein synthesis. The E. coli Hfq is structurally organized into two domains. An N-terminal domain that folds as strongly bent b-sheets within individual protomers to assemble into a typical toroidal hexameric ring. A C-terminal flexible domain, that encompasses about one-third of the protein, seems intrinsically unstructured. RNA binding function of Hfq mainly lies within its N-terminal core, whereas the function of the flexible domain remains controversial and largely unknown. Thanks to structural studies with biochemical and biophysical methods, we demonstrate that the Hfq C-terminal region has an intrinsic property to self-assemble into long amyloid-like fibrillar structures in vitro. We show that normal localization of Hfq within membrane-associated coiled structures in vivo requires this C-terminal domain. This finding establishes for the first time a function for the hitherto puzzling C-terminal Hfq region, with a plausible central role in RNA transactions and important consequences for the life of the bacterial cell.