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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 RNA 2020 ; 26 (12): 1976-1999 Nephropedia Template TP
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Physiologic RNA targets and refined sequence specificity of coronavirus EndoU #MMPMID32989044
Ancar R; Li Y; Kindler E; Cooper DA; Ransom M; Thiel V; Weiss SR; Hesselberth JR; Barton DJ
RNA 2020[Dec]; 26 (12): 1976-1999 PMID32989044show ga
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 ( downward arrow) A and C ( downward arrow) A sequences (endoY ( downward arrow) 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 (EndoU(mut)) or 2'-5' phosphodiesterase (PDE(mut)) 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 ( downward arrow) A and C ( downward arrow) A sequences (endoY ( downward arrow) A) within viral (+) strand RNA to evade dsRNA-activated host responses.