Feng Zhang on how transposons hijacked CRISPR

CRISPR pioneer Feng Zhang walked through his current research projects at the national meeting of the Italian Genetics Association (AGI) on September 24. CRISPR associated transposases, retrovirus-like particles repurposed as delivery vehicles, the ancestry of CRISPR systems, and more. The first issue is probably the most fascinating. It’s actually amazing to see a new activity performed by some CRISPR systems: not to protect bacteria from viruses, but to help transposons jump into specific genome sites.

Italian geneticist Michele Morgante asked Zhang about the evolutionary advantages of RNA-guided transposition. Why restrict their transpositional preference by hijacking an RNA-guided system that was aimed at something completely different? 

Zhang sees two potential reasons. “Number one, having a very, very active transposition system can be very toxic to the whole cell. But being able to be very precise about where inserting, especially if you’re precisely inserting to a benign spot in the genome, then the transposon can be very active, and still be well tolerated by the host. So I think that what the CRISPR system provides is specificity to minimize toxicity”.

The second reason, according to Zhang, is that “CRISPR systems often target mobile genetic elements, phages or plasmids. And this allows transposons to be more mobile, to be able to transpose onto mobile DNA, and then be more rapidly spread to other hosts”. Two pretty nice advantages, indeed.

Are RNA-guided transposons a phenomenon occurring only in prokaryotic cells? Any example of eukaryotic transposon working similarly? “There are interesting ones that we’re exploring”, said Zhang. “I think some of these mechanisms are likely conserved in eukaryotic cells”. 

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