The complexity of the RAS is far beyond we could suspect few years ago. There is growing evidence that changes in the novel components of the RAS [Ang-(1-7), ACE2, and Mas] may take part of the establishment and progression of cardiovascular and respiratory diseases. Importantly, these new components of the RAS, due to their counter regulatory actions, are candidates to serve as a concept to develop new cardiovascular and respiratory drugs. Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch Single-stranded RNAs (ssRNAs) are ubiquitous RNA elements that serve diverse functional roles. Much of our understanding of ssRNA conformational behavior is limited to structures in which ssRNA directly engages in tertiary interactions or is recognized by proteins. Little is known about the structural and dynamic behavior of free ssRNAs at atomic resolution. Here, we report the collaborative application of nuclear magnetic resonance (NMR) and replica exchange molecular dynamics (REMD) simulations to characterize the 12 nt ssRNA tail derived from the prequeuosine riboswitch. NMR carbon spin relaxation data and residual dipolar coupling measurements reveal a flexible yet stacked core adopting an A-form-like conformation, with the level of order decreasing toward the terminal ends. An A-to-C mutation within the polyadenine tract alters the observed dynamics consistent with the introduction of a dynamic kink. Pre-ordering of the tail may increase the efficacy of ligand binding above that achieved by a random-coil ssRNA. The REMD simulations recapitulate important trends in the NMR data, but suggest more internal motions than inferred from the NMR analysis. Our study unmasks a previously unappreciated level of complexity in ssRNA, which we believe will also serve as an excellent model system for testing and developing computational force fields. Single-stranded RNAs (ssRNAs), typically located at the ends of RNA hairpins and consisting of more than three unpaired residues, serve diverse structural and functional roles. They can fold onto neighboring RNA hairpins to form pseudoknots, essential architectural RNA elements involved in ribosomal frameshifting (1, 2) , hepatitis C internal ribosomal entry site (IRES) recognition (3, 4) and telomerase activity (5) . Messenger RNA (mRNA) degradation is prevented or promoted by 3 0 addition of a polyadenylated tail, which recruits essential protein cofactors (6) . Cleavage of the 5 0 transfer RNA (tRNA) leader by RNase P is a key step in tRNA maturation (7) . In riboswitches, ssRNA links the ligand-binding aptamer domain to the expression platform, providing the basis for communication between the two (8) (9) (10) .