title: Trying on tRNA for Size: RNase P and the T-box Riboswitch as Molecular Rulers.
abstract: Length determination is a fundamental problem in biology and chemistry. Numerous proteins measure distances on linear biopolymers to exert effects with remarkable spatial precision. Recently, ruler-like devices made of noncoding RNAs have been structurally and biochemically characterized. Two prominent examples are the RNase P ribozyme and the T-box riboswitch. Both act as molecular calipers. The two RNAs clamp onto the elbow of tRNA (or pre-tRNA) and make distance measurements orthogonal to each other. Here, we compare and contrast the molecular ruler characteristics of these RNAs. RNase P appears pre-configured to measure a fixed distance on pre-tRNA to ensure the fidelity of its maturation. RNase P is a multiple-turnover ribozyme, and its rigid structure efficiently selects pre-tRNAs, cleaves, and releases them. In contrast, the T-box is flexible and segmented, an architecture that adapts to the intrinsically flexible tRNA. The tripartite T-box inspects the overall shape, anticodon sequence, and aminoacylation status of an incoming tRNA while it folds co-transcriptionally, leading to a singular, conditional genetic switching event. The elucidation of the structures and mechanisms of action of these two RNA molecular rulers may augur the discovery of new RNA measuring devices in noncoding and viral transcriptomes, and inform the design of artificial RNA rulers.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, 50 South Drive, Bethesda, MD 20892, USA. adrian.ferre@nih.gov.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of RNA Biophysics and Cellular Physiology, National Heart, Lung and Blood Institute, 50 South Drive, Bethesda, MD 20892, USA. jinwei.zhang@nih.gov.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Ferré-DAmaré
mesh_terms: D009690:Nucleic Acid Conformation; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D043262:Ribonuclease P / Q000378:metabolism*; D058928:Riboswitch
chemical_list: D058928:Riboswitch; D012343:RNA, Transfer; D043262:Ribonuclease P
keywords: RNA structure; RNase P; T-box; interdigitated T-loops; molecular rulers; noncanonical base pairs; noncoding RNA; riboswitch; tRNA; tRNA elbow