Binary and ternary complexes of D. radioduransISDra2 TnpB crystallised by cryo-electron microscopy. Image courtesy of Nature. DOI: 10.1038/ s41586-023-05826-x

The structure of TnpB was determined by the group of Professor Guillermo Montoya at the Novo Nordisk Foundation Centre for Protein Research(CPR) at the University of Copenhagen and the group of Professor Virginijus iknys from Vilnius University Life Sciences Center(VU LSC).

In Nature, a small study titled “TnpB structure exposes the very little practical core of Cas12 nuclease household” was published.

Genome editing has been revolutionised by CRISPR-Cas nucleases including Cas9 and Cas12, often known as gene scissors. They allow for precise genome editing and the elimination of disease-causing mutations. Current gene therapy strategies rely on Adeno-associated viruses (AAV), but the size of Cas9 and Cas12 prevents them from being delivered to target cells this way.

TnpBs are a novel family of programmable nucleases discovered by researchers at the VU LSC; they are associated with transposons, which are mobile genetic elements. While they proved that TnpB is the smallest programmable nuclease, its structural organisation and system are still a mystery.

The recently published article in Nature is the fruit of years of dedicated study by Lithuanian scientists, proving their prowess in the area of life sciences and positioning them among the world’s best. Professor V. iknys comments, “This study has revealed the structure and system of TnpB gene scissors, which creates a basis for additional targeted engineering of the TnpB complex to transform it into a restorative tool for dealing with hereditary disease.”

In the current study, the authors used cryo-electron microscopy (cryo-EM) to determine the ternary structures of TnpB, the smallest programmable endonuclease, discussing how this gene-slicing enzyme recognises and precisely cuts DNA targets.

A lengthy RNA particle linked to the TnpB protein produces a complex three-dimensional structure that not only aids in recognising the DNA target but also regulates TnpB’s DNA-cutting activity, as shown by structural investigations. TnpB is the founding member of the Cas12 nuclease family, as determined via structural comparison and bioinformatic research.

Several factors, as noted by one of the article’s authors, Dr. Giedrius Sasnauskas, constituted the study’s success. “To begin with, the suitable research study item and the collaboration of biochemists, molecular biologists, bioinformaticians, and colleagues from NNF-CPR at the University of Copenhagen’s VU LSC. The scientist emphasises that they were able to conduct the research in Lithuania because to the cryo-electron microscope lense available at VU LSC.

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TnpB structure reveals just a small portion of the functional heart of the Cas12 nuclease family, as reported by Giedrius Sasnauskas et al. in Nature (2023). DOI: 10.1038/ s41586-023-05826-x

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Retrieved on May 4, 2023, from Reference: Snapshots of the smallest programmable nuclease TnpB disclosed (2023, May 4).

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