Type I-E CRISPR-Cas system as immune system in a eukaryote

Defense against viruses and other mobile genetic elements (MGEs) is important in many organisms. The CRISPR-Cas systems found in bacteria and archaea constitute adaptive immune systems that acquire the ability to recognize MGEs by introducing nucleic acid samples, spacers, in the CRISPR locus. The CRISPR is transcribed and processed, and the produced CRISPR RNAs guide Cas proteins to degrade matching nucleic acid sequences. No CRISPR-Cas system is found to occur naturally in eukaryotic cells but here we demonstrate interference by type I-E CRISPR-Cas system from Escherichia coli introduced in Saccharomyces cerevisiae. The designed CRISPR arrays are properly expressed and processed in S. cerevisiae. Targeted plasmids display reduced transformation efficiency, indicative of DNA cleavage. Unlike e.g. Cas9-based systems, which can be used to inactivate MGEs in eukaryotes by introducing specific mutations, type I-E systems processively degrade the target. The type I-E system thus allows for defense without knowledge of MGE gene function. The reconstituted CRISPR-Cas system in S. cerevisiae can also function as a basic research platform for testing the role of various factors in the interference process.