6533b861fe1ef96bd12c4642

RESEARCH PRODUCT

Single-Molecule FRET Reveals a Cooperative Effect of Two Methyl Group Modifications in the Folding of Human Mitochondrial tRNALys

Arthur Van AerschotAndrei Yu KobitskiKirsten DammertzMark HelmMark HelmMartin HengesbachSalifu Seidu-larryG. Ulrich NienhausG. Ulrich NienhausChristine S. Chow

subject

Models MolecularRNA StabilityMolecular Sequence DataClinical BiochemistryContext (language use)BiologyBiochemistryOrganophosphorus CompoundsDrug DiscoveryFluorescence Resonance Energy TransferHumansNucleotideMagnesiumTRNA foldingColoring AgentsMolecular Biologychemistry.chemical_classificationPharmacologyBase SequenceOligonucleotideRNAGeneral MedicineSingle-molecule FRETMitochondriaFolding (chemistry)chemistryBiochemistryTransfer RNABiophysicsNucleic Acid ConformationRNA Transfer LysMolecular MedicinePseudouridine

description

Summary Using a combination of advanced RNA synthesis techniques and single molecule spectroscopy, the deconvolution of individual contributions of posttranscriptional modifications to the overall folding and stabilization of human mitochondrial tRNA Lys is described. An unexpected destabilizing effect of two pseudouridines on the native tRNA folding was evidenced. Furthermore, the presence of m 2 G10 alone does not facilitate the folding of tRNA Lys , but a stabilization of the biologically functional cloverleaf shape in conjunction with the principal stabilizing component m 1 A9 exceeds the contribution of m 1 A alone. This constitutes an unprecedented cooperative effect of two nucleotide modifications in the context of a naturally occurring RNA, which may be of general importance for tRNA structure and help understanding several recently described decay pathways for hypomodified tRNAs.

10.1016/j.chembiol.2011.03.016http://dx.doi.org/10.1016/j.chembiol.2011.03.016