biostudies-literatureHansen LNNational Institutes of HealthNIGMS NIH HHS168070https://www.ebi.ac.uk/biostudies/studies/S-EPMC10152882biostudies-literatureUnknown435(10)The architecture and folding of complex RNAs is governed by a limited set of highly recurrent structural motifs that form long-range tertiary interactions. One of these motifs is the T-loop, which was first identified in tRNA but is broadly distributed across biological RNAs. While the T-loop has been examined in detail in different biological contexts, the various receptors that it interacts with are not as well defined. In this study, we use a cell-based genetic screen in concert with bioinformatic analysis to examine three different, but related, T-loop receptor motifs found in the flavin mononucleotide (FMN) and cobalamin (Cbl) riboswitches. As a host for different T-loop receptors, we employed the env8 class-II Cbl riboswitch, an RNA that uses two T-loop motifs for both folding and suJournal of molecular biologyContext-dependence of T-loop Mediated Long-range RNA Tertiary Interactions.PMC10152882R01 GM073850Kletzien OAUrquijo MHansen LNSchwanz LTBatey RTfalseContext-dependence of T-loop Mediated Long-range RNA Tertiary Interactions.The architecture and folding of complex RNAs is governed by a limited set of highly recurrent structural motifs that form long-range tertiary interactions. One of these motifs is the T-loop, which was first identified in tRNA but is broadly distributed across biological RNAs. While the T-loop has been examined in detail in different biological contexts, the various receptors that it interacts with are not as well defined. In this study, we use a cell-based genetic screen in concert with bioinformatic analysis to examine three different, but related, T-loop receptor motifs found in the flavin mononucleotide (FMN) and cobalamin (Cbl) riboswitches. As a host for different T-loop receptors, we employed the env8 class-II Cbl riboswitch, an RNA that uses two T-loop motifs for both folding and su2023-01-01T00:00:00Z2023 May2026-06-01T18:48:23.335Z2026-05-19T03:07:06.481ZS-EPMC101528823700346910.1016/j.jmb.2023.168070