So much has been written lately about the gene-editing system known as CRISPR/Cas9 and its potential to transform the field of biology that it’s easy to forget why the dynamic DNA/enzyme duo evolved in the first place —to protect bacteria from viral invaders known as bacteriophages by gathering chunks of their DNA into the bacterial genome. Now a study by scientists at Stanford, the University of Texas at Austin, the Carnegie Institution for Science and the University of Murcia, highlights the possibility that, at least in some types of bacteria, the CRISPR/Cas combo can also target RNA sequences. Their work is published today in Science.
Some background is necessary to understand the research: CRISPR stands for “clustered regularly interspaced short palindromic repeats,” and sequences interspersed within these repeats represent portions of invasive DNA from past infections that are squirreled away in the bacterial genome for future reference. DNA-chopping enzymes such as Cas9 are then used to cut the genomes of these invaders when they come knocking a second time.
As the CRISPR region fills with virus DNA, it becomes a molecular most-wanted gallery, representing the enemies the microbe has encountered. The microbe can then use this viral DNA to turn Cas enzymes into precision-guided weapons. The microbe copies the genetic material in each spacer into an RNA molecule. Cas enzymes then take up one of the RNA molecules and cradle it. Together, the viral RNA and the Cas enzymes drift through the cell. If they encounter genetic material from a virus that matches the CRISPR RNA, the RNA latches on tightly. The Cas enzymes then chop the DNA in two, preventing the virus from replicating.
A hint that CRISPR might also be able to obtain RNA sequences came from some unusual fusion genes discovered eight years ago by researchers in Calgary and Kyoto. But at the time the function of the fusions were a mystery. Stanford graduate student Sukrit Silas, Stanford geneticist Andrew Fire, PhD, and colleagues at the collaborating institutions recently found that the CRISPR system in some bacteria are indeed capable of capturing both RNA and DNA segments. This means that these bacteria could potentially expand their protective repertoire to include viruses with RNA-based genomes.
This reverse flow of information, from RNA to DNA, doesn’t happen very often. When it does, it’s usually mediated by the invader rather than the host (think HIV, which transcribes its RNA-based genome into DNA for insertion into the human genome to take advantage of its replication machinery and just generally hide out from host defense mechanisms). Now it seems that at least some bacteria have found a way to up the ante in an ongoing molecular battle between hosts and invaders. I can’t wait to see what happens next.
Previously: CRISPR critters and CRISPR conundrums, CRISPR marches forward: Stanford scientists optimize use in human blood cells and Cautious green light for CRISPR use in embryos in the U.K.; Stanford’s Hank Greely weighs in
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