title: Structural dynamics of a mitochondrial tRNA possessing weak thermodynamic stability.
abstract: Folding dynamics are ubiquitously involved in controlling the multivariate functions of RNAs. While the high thermodynamic stabilities of some RNAs favor purely native states at equilibrium, it is unclear whether weakly stable RNAs exist in random, partially folded states or sample well-defined, globally folded conformations. Using a folding assay that precisely tracks the formation of native aminoacylable tRNA, we show that the folding of a weakly stable human mitochondrial (hmt) leucine tRNA is hierarchical with a distinct kinetic folding intermediate. The stabilities of the native and intermediate conformers are separated by only about 1.2 kcal/mol, and the species are readily interconvertible. Comparison of folding dynamics between unmodified and fully modified tRNAs reveals that post-transcriptional modifications produce a more constrained native structure that does not sample intermediate conformations. These structural dynamics may thus be crucial for recognition by some modifying enzymes in vivo, especially those targeting the globular core region, by allowing access to pretransition state conformers. Reduced conformational sampling of the native, modified tRNAs could then permit improved performance in downstream processes of translation. More generally, weak stabilities of small RNAs that fold in the absence of chaperone proteins may facilitate conformational switching that is central to biological function.
authors: Department of Chemistry, Portland State University , 1825 SW Broadway, Portland Oregon 97209, United States.
authors: Hari
authors: H
authors: Bhaskaran
authors: Takaaki
authors: T
authors: Taniguchi
authors: Takeo
authors: T
authors: Suzuki
authors: Tsutomu
authors: T
authors: Suzuki
authors: John J
authors: JJ
authors: Perona
mesh_terms: D006801:Humans; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*; D013816:Thermodynamics
chemical_list: D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer