Transcripts of vaccinia virus postreplicative genes do not contain a 5' methylguanosine cap

Abstract

Vaccinia virus (VACV) is a prototypical poxvirus originally used for eradication of smallpox. Investigation into VACV mRNAs carried out almost half a century ago substantially contributed to the fundamental discovery of the 5 mRNA cap, a hallmark of all eukaryotic and many viral mRNAs. VACV research also facilitated the identification and understanding of the general mechanism of 5 mRNA cap synthesis. We characterized the VACV transcripts at the individual mRNA molecule level and found that vaccinia postreplicative mRNAs, containing nontemplated 5 poly(A) leaders, surprisingly lack the 5 cap structure in vivo. We also show that the lengths of the nontemplated leaders and the presence or absence of cap structures at the 5 mRNA ends are controlled by the initiator sequence of the VACV postreplicative promoters. One Sentence SummaryThe promoter sequence determines the synthesis of the 5 cap and poly(A) leaders in vaccinia virus postreplicative mRNAs.