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Physiologic RNA Targets and Refined Sequence Specificity of Coronavirus EndoU

ABSTRACT: Coronavirus EndoU inhibits double-stranded RNA (dsRNA)-activated antiviral responses; however, it is unclear how this occurs because 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

ORGANISM(S): Mus musculus

PROVIDER: GSE147852 | GEO | 2020/09/18

REPOSITORIES: GEO

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Physiologic RNA Targets and Refined Sequence Specificity of Coronavirus EndoU

Project description:Physiologic RNA Targets and Refined Sequence Specificity of Coronavirus EndoU

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Physiologic RNA targets and refined sequence specificity of coronavirus EndoU.

Project description: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.

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Transcriptome response of murine alveolar epithelial cells to infection by three unrelated respiratory viruses commonly studied in mouse models II

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