Abstract:
:Csm, a type III-A CRISPR-Cas interference complex, is a CRISPR RNA (crRNA)-guided RNase that also possesses target RNA-dependent DNase and cyclic oligoadenylate (cOA) synthetase activities. However, the structural features allowing target RNA-binding-dependent activation of DNA cleavage and cOA generation remain unknown. Here, we report the structure of Csm in complex with crRNA together with structures of cognate or non-cognate target RNA bound Csm complexes. We show that depending on complementarity with the 5' tag of crRNA, the 3' anti-tag region of target RNA binds at two distinct sites of the Csm complex. Importantly, the interaction between the non-complementary anti-tag region of cognate target RNA and Csm1 induces a conformational change at the Csm1 subunit that allosterically activates DNA cleavage and cOA generation. Together, our structural studies provide crucial insights into the mechanistic processes required for crRNA-meditated sequence-specific RNA cleavage, RNA target-dependent non-specific DNA cleavage, and cOA generation.
journal_name
Celljournal_title
Cellauthors
You L,Ma J,Wang J,Artamonova D,Wang M,Liu L,Xiang H,Severinov K,Zhang X,Wang Ydoi
10.1016/j.cell.2018.10.052subject
Has Abstractpub_date
2019-01-10 00:00:00pages
239-253.e16issue
1-2eissn
0092-8674issn
1097-4172pii
S0092-8674(18)31451-Xjournal_volume
176pub_type
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