After translation, transcription and genome replication which involve a single process (synthesis of (+) RNA) is realized. For the infecting (+) RNA to be replicated, multiple copies of (−) RNA must be transcribed and then used as templates for (+) RNA synthesis. Replicative intermediates (RIs) which are an association of RNA molecules consisting of a template RNA and several growing RNAs of varying length, are seen in both the replication complexes for (−) RNAs and (+) RNAs. For synthesis of each negative-strand and positive-strand RNAs, VPg protein in the poliovirus works as a primer. RNA-dependent RNA polymerase of the poliovirus adds two uracil nucleotides (UU) to VPg protein with utilizing the poly(A) tail at the 3′-end of the +ssRNA genome as a pattern, for synthesis of the negative-strand antigenomic RNA. To initiate this −ssRNA synthesis, the tyrosine hydroxyl of VPg is needed. But for the initiation of positive strand RNA synthesis, CRE-dependent VPg uridylylation is needed. Which means that VPg is once more utilized as a primer however this time it adds the two uridine triphosphates using a cis-acting replication element (CRE) as a template.