@article{Liao_Sharma_Svensson-Space_prior_CRISP-2022,
author = {Liao, Chunyu and Sharma, Sahil and Svensson, Sarah L. and 
          Kibe, Anuja and Weinberg, Zasha and Alkhnbashi, Omer S. and 
          Bischler, Thorsten and Backofen, Rolf and Caliskan, Neva and 
          Sharma, Cynthia M. and Beisel, Chase L.},
title = {Spacer prioritization in {CRISPR}-{Cas9} immunity is 
         enabled by the leader {RNA}},
journal = {Nat Microbiol},
year = {2022},
doi = {10.1038/s41564-022-01074-3},
volume = {7},
user = {backofen},
pmid = {35314780},
pages = {530-541},
number = {4},
issn = {2058-5276},
abstract = {CRISPR-Cas systems store fragments of foreign DNA, called 
            spacers, as immunological recordings used to combat future 
            infections. Of the many spacers stored in a CRISPR array, 
            the most recent are known to be prioritized for immune 
            defence. However, the underlying mechanism remains unclear. 
            Here we show that the leader region upstream of CRISPR 
            arrays in CRISPR-Cas9 systems enhances CRISPR RNA (crRNA) 
            processing from the newest spacer, prioritizing defence 
            against the matching invader. Using the CRISPR-Cas9 system 
            from Streptococcus pyogenes as a model, we found that the 
            transcribed leader interacts with the conserved repeats 
            bordering the newest spacer. The resulting interaction 
            promotes transactivating crRNA (tracrRNA) hybridization with 
            the second of the two repeats, accelerating crRNA 
            processing. Accordingly, disruption of this structure 
            reduces the abundance of the associated crRNA and immune 
            defence against targeted plasmids and bacteriophages. Beyond 
            the S. pyogenes system, bioinformatics analyses revealed 
            that leader-repeat structures appear across CRISPR-Cas9 
            systems. CRISPR-Cas systems thus possess an RNA-based 
            mechanism to prioritize defence against the most recently 
            encountered invaders.}
}