Nucleic Acids Research, Vol 25, Issue 10 2005-2011, Copyright © 1997 by Oxford University Press
R Schwartz and JF Curran
Others have recently shown that the UUU phenylalanine codon is highly
frameshift-prone in the 3'(rightward) direction at pyrimidine 3'contexts.
Here, several approaches are used to analyze frameshifting at such sites.
The four permutations of the UUU/C (phenylalanine) and CGG/U (arginine)
codon pairs were examined because they vary greatly in their expected
frameshifting tendencies. Furthermore, these synonymous sites allow direct
tests of the idea that codon usage can control frameshifting. Frameshifting
was measured for these dicodons embedded within each of two broader
contexts: the Escherichia coli prfB (RF2 gene) programmed frameshift site
and a 'normal' message site. The principal difference between these
contexts is that the programmed frameshift contains a purine-rich sequence
upstream of the slippery site that can base pair with the 3'end of 16 S
rRNA (the anti-Shine- Dalgarno) to enhance frameshifting. In both contexts
frameshift frequencies are highest if the slippery tRNAPhe is capable of
stable base pairing in the shifted reading frame. This requirement is less
stringent in the RF2 context, as if the Shine-Dalgarno interaction can help
stabilize a quasi-stable rephased tRNA:message complex. It was previously
shown that frameshifting in RF2 occurs more frequently if the codon 3'to
the slippery site is read by a rare tRNA. Consistent with that earlier
work, in the RF2 context frameshifting occurs substantially more frequently
if the arginine codon is CGG, which is read by a rare tRNA. In contrast, in
the 'normal' context frameshifting is only slightly greater at CGG than at
CGU. It is suggested that the Shine-Dalgarno-like interaction elevates
frameshifting specifically during the pause prior to translation of the
second codon, which makes frameshifting exquisitely sensitive to the rate
of translation of that codon. In both contexts frameshifting increases in a
mutant strain that fails to modify tRNA base A37, which is 3'of the
anticodon. Thus, those base modifications may limit frameshifting at UUU
codons. Finally, statistical analyses show that UUU Ynn dicodons are
extremely rare in E.coli genes that have highly biased codon usage.
ARTICLES
Analyses of frameshifting at UUU-pyrimidine sites
Department of Biology, Wake Forest University, PO Box 7325, Winston- Salem, NC 27109, USA.
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