Publications by authors named "D Lilley"

The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism.

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X-ray crystallography is a fundamental technique that provides atomic-level insights into RNA structures. However, obtaining crystals of RNA structures diffracting to high resolution is challenging. We introduce a simple strategy to enhance the resolution limit of RNA crystals by the selective substitution of Watson-Crick pairs by GU pairs within RNA sequences.

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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 reveals the crystal structure of a hammerhead ribozyme containing a pseudoknot, showing it closely resembles the pistol ribozyme in secondary structure.
  • The ribozyme's activity relies more on the presence of the G8 2'OH than on magnesium ions, suggesting similar catalytic mechanisms to the extended hammerhead but not to the pistol ribozyme.
  • The findings highlight that although the overall structure is alike, the cleavage site differs, allowing the PK hammerhead to maintain its unique mechanism and exhibit better activity compared to other hammerhead ribozymes.
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Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions.

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