Physiologic RNA targets and refined sequence specificity of coronavirus EndoU.

Ancar, Rachel; Li, Yize; Kindler, Eveline; Cooper, Daphne A; Ransom, Monica; Thiel, Volker; Weiss, Susan R; Hesselberth, Jay R; Barton, David J (2020). Physiologic RNA targets and refined sequence specificity of coronavirus EndoU. RNA - a publication of the RNA Society, 26(12), pp. 1976-1999. Cold Spring Harbor Laboratory Press 10.1261/rna.076604.120

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Kindler, Eveline Patricia and Thiel, Volker Earl

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1355-8382

Publisher:

Cold Spring Harbor Laboratory Press

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

08 Apr 2021 10:27

Last Modified:

08 Apr 2021 10:27

Publisher DOI:

10.1261/rna.076604.120

PubMed ID:

32989044

Uncontrolled Keywords:

coronavirus dsRNA endoribonuclease innate immunity mouse hepatitis virus

BORIS DOI:

10.7892/boris.152069

URI:

https://boris.unibe.ch/id/eprint/152069

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