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

Abstract

AbstractVaccinia 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.