The potential for long-range base pairing between the 5' and 3' ends o
f mRNA molecules was examined for 134 Drosophila and 204 human sequenc
es collected from the GenBank database. Each sequence was divided into
two parts, a 5' sequence taken from the start of the protein-encoding
region and a 3' sequence taken from the end of the transcript. The st
rongest RNA pairing stem between each pair of 5' and 3' sequences was
identified and scored using an alignment program modified to incorpora
te RNA base pairing. The observed pairing scores were then compared wi
th a random distribution of scores generated by aligning each 5' seque
nce to random permutations of its corresponding 3' sequence. For both
the Drosophila and the human mRNAs, the observed pairing scores were s
ignificantly biased toward the upper tail of the random distributions,
with 61% of the Drosophila sequences and 64% of the human sequences f
alling within the upper half of the random distributions. This suggest
s that a pattern of long-range base pairing may be a common feature of
eukaryotic mRNAs. We have also analyzed a subset of Drosophila and hu
man mRNAs which show the greatest potential for long-range pairing. Th
e human pairings appear to be stronger and localized to more specific
regions near the ends of the mRNA sequence than those of Drosophila.