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Berkeley Scientists Show How Type III CRISPR/Cas System Targets RNA

NEW YORK (GenomeWeb) – CRISPR could soon be turned into an RNA editing tool, as well as a genome editing tool. Scientists from the University of California, Berkeley, led by CRISPR/Cas9 pioneer Jennifer Doudna, have detailed in a recent Science paper the protein structure that allows a RNA-targeting variant of CRISPR/Cas to cleave single-stranded RNA.

There are three known types of RNA-guided CRISPR/Cas systems: Type I and Type II CRISPR/Cas surveillance complexes target double-stranded DNA, while Type III complexes, the subject of the publication, target single-stranded RNA.

"We have provided the first high-resolution structural images of a fully intact Type III CRISPR-Cas surveillance complex and the first picture of how the RNA-targeting mechanism of this complex might work," Eva Nogales, a leading authority on electron microscopy and co-senior author of the paper, said in a statement.

Using cryo-electron microscopy, the scientists revealed thumb-like protein domains in the Type III CRISPR/Cas complex that allows the system to latch on to RNA, which could be invasive nucleic acid from phages that the bacteria degrades.

The protein domains showed an architectural similarity to similar domains in Type I CRISPR/Cas systems that target DNA. "This suggests a divergent evolution of these adaptive immune systems from a common ancestor," said David Taylor, a lead author of the study.

But the Type III CRISPR-Cas system could be more than just a phylogenetic differentiator.

"Our structural data suggests ways in which this RNA-targeting CRISPR/Cas complex could potentially be re-purposed for RNA-interference applications," Doudna said, though she did not specify what those applications might be.