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Related Concept Videos

RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...
Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...

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DNAzyme-dependent Analysis of rRNA 2’-O-Methylation
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A modified X10-23 DNAzyme that can better access large, structured RNA targets.

Connor Nurmi1,2, Halle M Barber3, Harneesh Kaur3

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Ontario L8S 4L8, Canada.

Nucleic Acids Research
|January 7, 2026
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Summary

A novel 10-23 DNA enzyme, XdZ-2, utilizes modified nucleic acids (XNAs) to efficiently cleave large, structured RNA (lsRNA) targets like those from SARS-CoV-2, offering improved activity and stability.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Therapeutics

Background:

  • The 10-23 DNA enzyme is highly efficient at cleaving RNA but struggles with large, structured RNA (lsRNA) targets.
  • Modifications like Xeno nucleic acids (XNAs) and antisense DNA oligonucleotides (ASOs) have been explored to improve accessibility but present limitations.
  • Current strategies face challenges in balancing accessibility, cleavage efficiency, and product release for lsRNA.

Purpose of the Study:

  • To develop an improved 10-23 DNA enzyme variant with enhanced accessibility and activity against lsRNA targets.
  • To investigate the efficacy of incorporating specific XNA patterns into the substrate recognition arms of the 10-23 enzyme.
  • To evaluate the performance of the novel enzyme variant against SARS-CoV-2 lsRNA targets.

Main Methods:

  • Designed and synthesized a novel 10-23 enzyme variant (XdZ-2) featuring a specific 2'F-RNA-LNA-FANA arm pattern.
  • Tested the cleavage activity of XdZ-2 against various lsRNA targets from SARS-CoV-2.
  • Compared the performance of XdZ-2 with the unmodified X10-23 enzyme and ASO strategies.

Main Results:

  • XdZ-2 demonstrated significantly enhanced cleavage rates, up to 82-fold faster than X10-23 for a specific SARS-CoV-2 lsRNA target.
  • The XdZ-2 enzyme showed improved accessibility to lsRNA targets compared to the X10-23 variant.
  • While ASO strategies showed higher rates in some cases, XdZ-2 offered advantages in low Mg2+ conditions and product release.

Conclusions:

  • The XdZ-2 enzyme represents a promising advancement in RNA-cleaving technology for targeting lsRNA.
  • XdZ-2 offers a potential alternative to existing methods, particularly in challenging biological environments.
  • This modified enzyme holds potential for applications in RNA therapeutics and diagnostics, especially against viral targets like SARS-CoV-2.