Catalytic RNAs, or ribozymes, catalyze diverse chemical reactions that could have sustained primordial life in the hypothetical RNA world. Many natural ribozymes and laboratory evolved ribozymes exhibit efficient catalysis mediated by elaborate catalytic cores within complex tertiary structures. However, such complex RNA structures and sequences are unlikely to have emerged by chance during the earliest phase of chemical evolution. Here, we explored simple and small ribozyme motifs capable of ligating two RNA fragments in a template-directed fashion (ligase ribozymes). One-round selection of small ligase ribozymes followed by deep sequencing revealed a ligase ribozyme motif comprising a three-nucleotide loop opposite to the ligation junction. The observed ligation was magnesium(II) dependent and appears to form a 2'-5' phosphodiester linkage. The fact that such a small RNA motif can function as a catalyst supports a scenario in which RNA or other primordial nucleic acids played a central role in chemical evolution of life.
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http://dx.doi.org/10.1038/s41598-023-35584-9 | DOI Listing |
RSC Chem Biol
December 2024
Department of Chemistry, Texas A&M University College Station Texas 77843 USA
Despite the growing interest in mirror-image l-oligonucleotides, both as a robust nucleic acid analogue and as an artificial genetic polymer, their broader adoption in biochemical research and medicine remains hindered by challenges associated with the synthesis of long sequences, especially for l-RNA. Herein, we present a novel strategy for assembling long l-RNAs the joining of two or more shorter fragments using cross-chiral ligase ribozymes together with new substrate activation chemistry. We show that 5'-monophosphorylated l-RNA, which is readily prepared by solid-phase synthesis, can be activated by chemical attachment of a 5'-adenosine monophosphate (AMP) or diphosphate (ADP), yielding 5'-adenosyl(di- or tri-)phosphate l-RNA.
View Article and Find Full Text PDFRedox Biol
February 2025
China National Center for Bioinformation, Beijing, 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:
Lactate-mediated lactylation on target proteins is recently identified as the novel posttranslational modification with profound biological functions. RNA 5-methylcytosine (mC) modification possesses dynamic and reversible nature, suggesting that activity of its methyltransferase NSUN2 is actively regulated. However, how NSUN2 activity is response to acidic condition in tumor microenvironment and then regulates cancer cell survival remain to be clarified.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
The Salk Institute, La Jolla, CA 92037.
An RNA ligase ribozyme that catalyzes the joining of RNA molecules of the opposite chiral handedness was optimized for the ability to synthesize its own enantiomer from two component fragments. The mirror-image D- and L-ligases operate in concert to provide a system for cross-chiral replication, whereby they catalyze each other's synthesis and undergo mutual amplification at constant temperature, with apparent exponential growth and a doubling time of about 1 h. Neither the D- nor the L-RNA components alone can achieve autocatalytic self-replication.
View Article and Find Full Text PDFNat Rev Chem
December 2024
Department of Chemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan.
In the canonical genetic code, the 61 sense codons are assigned to the 20 proteinogenic amino acids. Advancements in genetic code manipulation techniques have enabled the ribosomal incorporation of nonproteinogenic amino acids (npAAs). The critical molecule for translating messenger RNA (mRNA) into peptide sequences is aminoacyl-transfer RNA (tRNA), which recognizes the mRNA codon through its anticodon.
View Article and Find Full Text PDFJ Physiol Pharmacol
August 2024
Department of Pharmacology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
The lipid peroxidation product 4-hydroxynonenal (HNE) may be involved in vascular endothelial cell damage by induction of oxidative stress, apoptosis, and loss of redox homeostasis. There is evidence that stimulation of endothelial cells with 4-HNE induces the activation of the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) pathway. Sestrin2 protein (SESN2) is one of the key regulators of Nrf2 and is involved in the cellular response to oxidative stress.
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