If there’s an official analogy for Cas9, it’s a pair of molecular scissors. Give Cas9 an RNA guide, and it will hunt down the complementary DNA and slice it in two with surgical precision. However, in this, the age of multitasking (HEY! Put down that other screen and pay attention!), being a one-trick pony doesn’t always cut it. Indeed, it turns out two new CRISPR upstarts – Cpf1 and C2c2 – not only slice targets, they also dice natural CRISPR arrays, making them multitasking Swiss Army knives to Cas9’s single-purpose shears.
Natural CRISPR guide RNAs come in long arrays, and after the whole array is transcribed, it must be diced up to release the individual guides. Cas9 relies on other players, including a tracRNA and an RNase, to do this dicing, but other CRISPR effectors seem to show a bit more versatility.
Recently, Bernd Zetsche, in Feng Zhang’s lab at MIT, and Ines Fonfara, in Emmanuelle Charpentier’s lab at the Max Planck Institute, showed that Cpf1 dices up multiplex CRISPR arrays in vitro and in vivo, before using the newly processed guide RNAs to target DNA. Like a Swiss Army knife flipping out different tools, Cpf1 even uses separate domains to do its DNA slicing and CRISPR array dicing.
Now, it turns out another CRISPR effector, the RNA-targeting C2c2, also boasts both slicing and dicing skills. Working with Jennifer Doudna at UC Berkeley, Alexandra East-Seletsky showed that C2c2 processes its own CRISPR arrays like Cpf1. Also like Cpf1, C2c2 uses a separate domain for RNA array dicing, even though its slicing targets the same type of molecule as its dicing; i.e., RNA.
Since natural CRISPR arrays are very compact, these array dicing CRISPR effectors could be very useful for target multiplexing. Indeed, another preprint from Bernd Zetsche just popped up on bioRxiv using Cpf1 for multiplex gene editing in mice.
If you want to try some multi-tasking yourself, just pull that other screen back out and point it to Nature, 2016.