Year: 2026
Type: preprint
Abstract: SUMMARY Comparative genomics has identified over 1,000 candidate structured RNA motifs, yet most remain functionally uncharacterized. Here, we combine crystallography, comparative analysis, and bacterial genetics to identify three families of bacterial tRNA-like RNAs. The skipping-rope RNA adopts an L-shaped fold resembling tRNA despite distinct secondary-structure connectivity and tertiary interactions. In Clostridioides difficile , the skipping-rope RNA RCd1 is abundantly expressed and processed into a highly stable RNA species. RCd1 overexpression suppresses sporulation, whereas its deletion enhances early spore formation, supporting a role in sporulation control. Guided by the skipping-rope structure, we identify a conserved architectural core and use it to recognize additional candidate tRNA mimics. Crystal structures of DUF2693-FD and salivarius-1 RNAs confirm a shared tRNA-like scaffold assembled through distinct interaction networks. Together, these findings expand the repertoire of bacterial tRNA mimics and establish a structural framework for recognizing shared architectures among uncharacterized ncRNAs, linking one such family to bacterial developmental regulation.
Institutions: University of Dundee, Shenzhen Technology University, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut de Biologie Intégrative de la Cellule, Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Architecture et Réactivité de l'arN, Institut de Biologie Moléculaire et Cellulaire, Wenzhou Institute, University of Chinese Academy of Sciences, Université de Strasbourg, Institut Universitaire de France
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Idex Paris-Saclay, Role of c-di-GMP in the riboswitch and antisense RNA-mediated control of cellular processes associated with community behaviour in Clostridium difficile, a bacterium responsible for nosocomial infections, Tackling antibiotic resistance by targeting toxin antitoxin system, Role of RNA-dependent control in the pathophysiology of Clostridioides difficile and its interaction with the host, G6377091821, G7500324270
OpenAlex ID: W7223068874
