Publications by authors named "J A Piccirilli"

Article Synopsis
  • - RNA-Puzzles is a collaborative project focused on improving the prediction of RNA three-dimensional structures, with predictions made by modeling groups before experimental structures are published.
  • - A significant set of predictions was made by 18 groups for 23 different RNA structures, including various elements like ribozymes and aptamers.
  • - The study highlights key challenges in RNA modeling, such as identifying helix pairs and ensuring proper stacking, and notes that some top-performing groups also excelled in a separate competition (CASP15).
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Small-molecule RNA binders have emerged as an important pharmacological modality. A profound understanding of the ligand selectivity, binding mode, and influential factors governing ligand engagement with RNA targets is the foundation for rational ligand design. Here, we report a novel class of coumarin derivatives exhibiting selective binding affinity towards single G RNA bulges.

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MTR1 is an in vitro-selected alkyl transferase ribozyme that transfers an alkyl group from -alkylguanine to N1 of the target adenine in the RNA substrate (A63). The structure of the ribozyme suggested a mechanism in which a cytosine (C10) acts as a general acid to protonate -alkylguanine N1. Here, we have analyzed the role of the C10 general acid and the A63 nucleophile by atomic mutagenesis and computation.

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Article Synopsis
  • * The study found that N-methylation of guanosine at position 9 (mG9) stabilizes wild-type mt-Leu(UAA) tRNA but destabilizes certain pathogenic variants associated with MELAS.
  • * Findings suggest that modifying the methylation level of mt-tRNAs could be a potential therapeutic approach for mt-tRNA-related diseases by impacting their stability and functionality.
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Coded ribosomal peptide synthesis could not have evolved unless its sequence and amino acid-specific aminoacylated tRNA substrates already existed. We therefore wondered whether aminoacylated RNAs might have served some primordial function prior to their role in protein synthesis. Here, we show that specific RNA sequences can be nonenzymatically aminoacylated and ligated to produce amino acid-bridged stem-loop RNAs.

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