Physiologic RNA targets and refined sequence specificity of coronavirus EndoU.
RNA
; 26(12): 1976-1999, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-973202
ABSTRACT
Coronavirus EndoU inhibits dsRNA-activated antiviral responses; however, the physiologic RNA substrates of EndoU are unknown. In this study, we used mouse hepatitis virus (MHV)-infected bone marrow-derived macrophage (BMM) and cyclic phosphate cDNA sequencing to identify the RNA targets of EndoU. EndoU targeted viral RNA, cleaving the 3' side of pyrimidines with a strong preference for U ↓ A and C ↓ A sequences (endoY ↓ A). EndoU-dependent cleavage was detected in every region of MHV RNA, from the 5' NTR to the 3' NTR, including transcriptional regulatory sequences (TRS). Cleavage at two CA dinucleotides immediately adjacent to the MHV poly(A) tail suggests a mechanism to suppress negative-strand RNA synthesis and the accumulation of viral dsRNA. MHV with EndoU (EndoUmut) or 2'-5' phosphodiesterase (PDEmut) mutations provoked the activation of RNase L in BMM, with corresponding cleavage of RNAs by RNase L. The physiologic targets of EndoU are viral RNA templates required for negative-strand RNA synthesis and dsRNA accumulation. Coronavirus EndoU cleaves U ↓ A and C ↓ A sequences (endoY ↓ A) within viral (+) strand RNA to evade dsRNA-activated host responses.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA
/
Viral Nonstructural Proteins
/
Murine hepatitis virus
/
Uridylate-Specific Endoribonucleases
Type of study:
Diagnostic study
Limits:
Animals
Language:
English
Journal:
RNA
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
RNA.076604.120
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