The minus-strand genome of Sendai virus is an assembly of the
nucleocapsid protein (N) and RNA, in which each N subunit is
associated with precisely 6 nt. Only genomes that are a multiple
of 6 nt long replicate efficiently or are found naturally, and
their replication promoters contain sequence elements with hexamer
repeats. Paramyxoviruses that are governed by this hexamer rule
also edit their P gene mRNA during its synthesis, by G insertions,
via a controlled form of viral RNA polymerase
“stuttering” (pseudo-templated transcription). This
stuttering is directed by a cis-acting sequence (3′
UNN UUUUUU CCC), whose hexamer phase is conserved within
each virus group. To determine whether the hexamer phase of
a given nucleotide sequence within nucleocapsids affected its
sensitivity to chemical modification, and whether hexamer phase
of the mRNA editing site was important for the editing process,
we prepared a matched set of viruses in which a model editing
site was displaced 1 nt at a time relative to the genome ends.
The relative abilities of these Sendai viruses to edit their
mRNAs in cell culture infections were examined, and the ability
of DMS to chemically modify the nucleotides of this
cis-acting signal within resting viral nucleocapsids
was also studied. Cytidines at hexamer phases 1 and 6 were the
most accessible to chemical modification, whereas mRNA editing
was most extensive when the stutter-site C was in positions
2 to 5. Apparently, the N subunit imprints the nucleotide sequence
it is associated with, and affects both the initiation of viral
RNA synthesis and mRNA editing. The N-subunit assembly thus
appears to superimpose another code upon the genetic code.