mRNA poly(A)-tail length is a battleground for coronavirus-host competition

Abstract

Most eukaryotic mRNAs contain a poly(A) tail, which in post-embryonic cells enhances their stability. Many cytoplasmic RNA viruses also harbor poly(A) tails on their genomic RNA and mRNAs. Here, we report that coronavirus infection causes cytoplasmic poly(A)-binding protein (PABPC) activity to become limiting, which preferentially destabilizes short-tailed host mRNAs, occurring before the action of virally encoded mRNA-decay factor nsp1. In this environment hostile to poly(A) tails, viral RNAs maintain a narrow tail-length distribution centering on 70-80 nucleotides across infection cycles. They do this through two mechanisms. First, viral tails are extended during RNA synthesis within double-membrane vesicles; second, viral tails are capped by a complex that includes PABPC1 and CSDE1 and slows tail shortening. Our findings suggest poly(A)-tail length is an arena of host- virus conflict, in which preserving tail lengths of viral mRNAs promotes their cytoplasmic dominance. HighlightsO_LIPABPC1 becomes limiting during coronavirus infection C_LIO_LILimiting PABPC1 promotes decay of short-tailed host mRNAs--independently of nsp1 C_LIO_LIThe tail lengths of coronaviral mRNAs are extended during their synthesis in DMVs C_LIO_LIViral tails are capped by PABPC1 and CSDE1, which protects against deadenylation C_LI