RNA-catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme. We found that diamidophosphate (DAP) and imidazole drive the formation of 2',3'-cyclic phosphate RNA mono- and oligonucleotides from monophosphorylated precursors in frozen water-ice. This long-lived activation enables iterative enzymatic assembly of long RNAs. Our results provide a plausible scenario for the generation of higher-energy substrates required to fuel ribozyme-catalyzed RNA synthesis in the absence of a highly evolved metabolism.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898671PMC
http://dx.doi.org/10.1002/anie.202010918DOI Listing

Publication Analysis

Top Keywords

rna substrates
8
rna
7
prebiotically plausible
4
plausible rna
4
rna activation
4
activation compatible
4
compatible ribozyme-catalyzed
4
ribozyme-catalyzed ligation
4
ligation rna-catalyzed
4
rna-catalyzed rna
4

Similar Publications

Biomimetic fluorescence-enhanced platform based on photonic crystals and DNAzyme walker for visualization and quantification of miRNA-21.

Talanta

December 2024

Institute of Biomedical Precision Testing and Instrumentation, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan, Shanxi, 030600, PR China.

Developing a fluorescence sensing platform for point-of-care detection of low abundance biomarkers is highly valuable for early diagnosis of disease. Herein, a biomimetic fluorescence-enhanced platform based on photonic crystals and DNAzyme walker was constructed and further applied to visualize and quantify the miRNA-21 in biological samples. The DNAzyme walker was orthogonally activated by the target miRNA-21, which enabled the unlocking of the DNAzyme walker strand and the subsequently repeated substrate cleavage, thus generating enhanced fluorescence signals.

View Article and Find Full Text PDF

Millions of tons of polyethylene terephthalate (PET) are produced each year, however only ~30% of PET is currently recycled in the United States. Improvement of PET recycling and upcycling practices is an area of ongoing research. One method for PET upcycling is chemical depolymerization (through hydrolysis or aminolysis) into aromatic monomers and subsequent biodegradation.

View Article and Find Full Text PDF

Background: Fervidobacterium is a genus of thermophilic anaerobic Gram-negative rod-shaped bacteria belonging to the phylum Thermotogota. They can grow through fermentation on a wide range of sugars and protein-rich substrates. Some can also break down feather keratin, which has significant biotechnological potential.

View Article and Find Full Text PDF

Advances of NAT10 in diseases: insights from dual properties as protein and RNA acetyltransferase.

Cell Biol Toxicol

December 2024

Department of Laboratory Medicine, Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, Guangdong, China.

N-acetyltransferase 10 (NAT10) is a member of the Gcn5-related N-acetyltransferase (GNAT) family and it plays a crucial role in various cellular processes, such as regulation of cell mitosis, post-DNA damage response, autophagy and apoptosis regulation, ribosome biogenesis, RNA modification, and other related pathways through its intrinsic protein acetyltransferase and RNA acetyltransferase activities. Moreover, NAT10 is closely associated with the pathogenesis of tumors, Hutchinson-Gilford progeria syndrome (HGPS), systemic lupus erythematosus, pulmonary fibrosis, depression and host-pathogen interactions. In recent years, mRNA acetylation has emerged as a prominent focus of research due to its pivotal role in regulating RNA stability and translation.

View Article and Find Full Text PDF

Despite the remarkable resistance of the nucleic acid phosphodiester backbone to degradation affording genetic stability, the P-O bond must be broken during DNA repair and RNA metabolism, among many other critical cellular processes. Nucleases are powerful enzymes that can enhance the uncatalyzed rate of phosphodiester bond cleavage by up to ∼10-fold. Despite the most well accepted hydrolysis mechanism involving two metals (M to activate a water nucleophile and M to stabilize the leaving group), experimental evidence suggests that some nucleases can use a single metal to facilitate the chemical step, a controversial concept in the literature.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!