Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U.
Nucleic Acids Res
; 49(17): 10136-10149, 2021 09 27.
Article
in English
| MEDLINE | ID: covidwho-1359701
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Nsp15 is a uridine specific endoribonuclease that coronaviruses employ to cleave viral RNA and evade host immune defense systems. Previous structures of Nsp15 from across Coronaviridae revealed that Nsp15 assembles into a homo-hexamer and has a conserved active site similar to RNase A. Beyond a preference for cleaving RNA 3' of uridines, it is unknown if Nsp15 has any additional substrate preferences. Here, we used cryo-EM to capture structures of Nsp15 bound to RNA in pre- and post-cleavage states. The structures along with molecular dynamics and biochemical assays revealed critical residues involved in substrate specificity, nuclease activity, and oligomerization. Moreover, we determined how the sequence of the RNA substrate dictates cleavage and found that outside of polyU tracts, Nsp15 has a strong preference for purines 3' of the cleaved uridine. This work advances our understanding of how Nsp15 recognizes and processes viral RNA, and will aid in the development of new anti-viral therapeutics.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Uridine
/
RNA, Viral
/
Viral Nonstructural Proteins
/
Endoribonucleases
/
SARS-CoV-2
Type of study:
Experimental Studies
Limits:
Humans
Language:
English
Journal:
Nucleic Acids Res
Year:
2021
Document Type:
Article
Affiliation country:
Nar
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