Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element

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Abstract
Genomes and antigenomes of many positive-strand RNA viruses contain 3'-poly(A) and 5'-poly(U) tracts, respectively, serving as mutual templates. Mechanism(s) controlling the length of these homopolymeric stretches are not well understood. Here, we show that in coxsackievirus B3 (CVB3) and three other enteroviruses the poly(A) tract is approximately 80-90 and the poly(U) tract is approximately 20 nt-long. Mutagenesis analysis indicate that the length of the CVB3 3'-poly(A) is determined by the oriR, a cis-element in the 3'-noncoding region of viral RNA. In contrast, while mutations of the oriR inhibit initiation of (-) RNA synthesis, they do not affect the 5'-poly(U) length. Poly(A)-lacking genomes are able to acquire genetically unstable AU-rich poly(A)-terminated 3'-tails, which may be generated by a mechanism distinct from the cognate viral RNA polyadenylation. The aberrant tails ensure only inefficient replication. The possibility of RNA replication independent of oriR and poly(A) demonstrate that highly debilitated viruses are able to survive by utilizing 'emergence', perhaps atavistic, mechanisms.