mRNA Destabilization: The Role of the 3?UTR in Post-transcriptional Regulation of Wnt8 Transcripts
Abstract
wnt8 is essential for normal embryonic development in vertebrates: severe
developmental malformations occur when wnt8 is either over- or under- expressed.
Therefore, wnt8 has to be activated at a specific time and for a specific duration to
promote proper development. While Wnt8 signaling is regulated at several levels, factors
that regulate the extent or duration of Wnt8 signaling are not well understood. One
possible mechanism is through the action of microRNAs (miRNAs), 21-22 bp oligomers
that are complementary to particular mRNA binding sites found in the 3' untranslated
regions (3' UTRs) of target transcripts. The binding of miRNAs to specific sites in
mRNAs causes one of two fates: the mRNA is degraded or translation of the transcript is
suppressed. The zebrafish wnt8 locus is complex and produces transcripts with
alternative 3' UTR elements, each of which has several putative miRNA binding sites.
To advance our understanding of wnt8 regulation, we are testing whether the zebrafish
wnt8 3'UTR elements destabilize wnt8 transcripts, and we will pinpoint the UTR sequences that mediate this function. Our results indicate that the zebtrafish wnt8 3'
UTRs destabilize transcripts in a similar fashion and in a sequence dependent manner.
This mode of regulation is not tissue restricted. By making deletions, it was found that
one of these alternate 3' UTRs contains much of its activity within a 5' portion that is
120 nucleotides in length. However, this portion does not recapitulate all of the UTR
activity which is indicative of a synergistic effect of multiple regulatory elements such as
through miRNAs.
Citation
Butler, Annika D 1987- (2010). mRNA Destabilization: The Role of the 3?UTR in Post-transcriptional Regulation of Wnt8 Transcripts. Honors and Undergraduate Research. Available electronically from https : / /hdl .handle .net /1969 .1 /ETD -TAMU -2010 -05 -8120.