THE 5'-ENDS OF HANTAAN VIRUS (BUNYAVIRIDAE) RNAS SUGGEST A PRIME-AND-REALIGN MECHANISM FOR THE INITIATION OF RNA-SYNTHESIS

We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to ga in insight into the manner in which these chains were initiated. Like those of all members of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal extensions that were heterogeneous in both length and sequence, presumably because HTN also ''cap snatches'' host mRNAs to initiate the viral mRNAs. Unexpectedly however, almost ah of the mRNAs contained a G residue at position -1, and a large frac tion also lacked precisely one of the three UAG repeats at the termini . The genomes, on the other hand, commenced with a U residue at positi on +1, but only 5' monophosphates were found here, indicating that the se chains may not have initiated with UTP at this position. Taken toge ther, these unusual findings suggest a prime-and-realign mechanism of chain initiation in which mRNAs are initiated with a G-terminated host cell primer and genomes with GTP, not at the 3' end of the genome tem plate but internally (opposite the template C at position +3), and aft er extension by one or a few nucleotides, the nascent chain realigns b ackwards by virtue of the terminal sequence repeats, before processive elongation takes place. For genome initiation, an endonuclease, perha ps that involved in cap snatching, is postulated to remove the 5' term inal extension of the genome, leaving the 5' pU at position +1.