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

Mark J.M. van Ooij, Charlotta Polacek, Dirk H.R.F. Glaudemans, Judith Kuijpers, Frank J.M. van Kuppeveld, Raul Andino, Vadim I. Agol, Willem J.G. Melchers

Research output: Contribution to journalJournal articleResearchpeer-review

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 80–90 and the poly(U) tract is 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.
Original languageEnglish
JournalNucleic Acids Research
Volume34
Issue number10
Pages (from-to)2953-2965
ISSN0305-1048
DOIs
Publication statusPublished - 2006
Externally publishedYes

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