China Identifies New TIGR System With Gene-Editing ‘RNA Switch’

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Chinese researchers have elucidated the mechanism of a new gene-editing system that can precisely control how DNA is cleaved through guide RNA (gRNA).

According to Chinese biotechnology news outlet BioOn, a research team led by Professor Zhang Heng of Tianjin Medical University published the findings in the international journal Molecular Cell on the 2nd (local time).

The team revealed the molecular-level mechanism of the TIGR-TasH system, which uses the TasH protein within the TIGR (Tandem Interspersed Guide RNA) gene-editing system. Unlike CRISPR-Cas, the TIGR system uses guide RNA (tigRNA) containing dual spacer sequences to recognize both strands of target DNA.

The researchers analyzed six cryo-electron microscopy (cryo-EM) structures of the TIGR-TasH complex derived from the Salicola phage. They confirmed that the TasH protein processes precursor tigRNA on its own, binds to target DNA and then cleaves the DNA through its HNH nuclease domain.

In particular, they found that the conserved “box C motif” in tigRNA binds to a specific base, adenine, stabilizing the structure involved in DNA cleavage. Unlike conventional approaches that modify proteins, this finding indicates that a nickase—an enzyme that cuts only one strand of the DNA double helix—can be created through guide RNA design.

The study not only elucidated the diverse operating modes of the TIGR system but also provided a structural blueprint for developing new base-editing technologies based on multiplex gene editing or nickases, according to the researchers. The TIGR system has strong application potential because of its small size and ability to function without a specific base sequence (PAM).