FASEB. J. (1998) 12, A1453. Abstract #828.
LOADING 0F EBNA-1 mRNA AVOIDS SENSE-ANTISENSE "COLLISIONS".
A. D. Cristillo, T. P. Lillicrap and D. R. Forsdyke. Dept.
Biochem., Queen's University, Kingston, Ontario, Canada K7L3N6
In the 1960's
Szybalski showed that mRNA-synonymous strands of DNA have purine-rich
clusters, and Chargaff presented his second parity rule that, to a close
approximation, %A=%T and %C=%G for single DNA strands. We report
that small deviations from the rule (%R>%Y in mRNA-synonymous
strands) allow determination of transcription direction for the majority
of genes in many species (Bell & Forsdyke, unpublished work; Dang et
al. 1998, Biochem. Cell Biol. in press). Purine clusters in
an mRNA correspond to the loop domains of potential stem-loop
structures, which, by virtue of being enriched with non-complementary
bases, should avoid loop-loop "kissing" interactions with
other mRNAs in the same cell. However,
most genes of CG-rich viruses with a high commitment to latency (HTLV-1,
Epstein-Barr) disobey the transcription direction rule (%Y>%R). Thus,
the viruses have pyrimidine clusters in the loop domains of potential
RNA stem-loop structures. By "driving on the wrong side of the
road" they invite sense-antisense RNA "collisions" with
host mRNAs, thus triggering the interferon response and increasing MHC
protein expression. However, the only gene transcribed during the
"EBNA-1 only program" of viral latency is "polite"
(%R>%Y). This purine-loading requires the protein to carry a
non-functional (GlyAla) simple-sequence domain.
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This page was last edited on 08 Nov 2010 by Donald Forsdyke