Developmental Regulation of bicoid mRNA Stability Is Mediated by the First 43 Nucleotides of the 3′ Untranslated Region

Abstract

During the transition from the maternal to the zygotic developmental program, the expression of genes important for pattern formation or cell cycle regulation changes dramatically. Rapid changes in gene expression are achieved in part through the control of mRNA stability. This report focuses on bicoid, a gene essential for formation of anterior embryonic structures in Drosophila melanogaster. bicoid mRNA is synthesized exclusively during oogenesis. Here, we show that bicoid mRNA stability is regulated. While bicoid mRNA is stable in retained oocytes, in unfertilized eggs, and during the first 2 h of embryogenesis, specific degradation is activated at cellularization of the blastoderm. To identify cis-acting sequences required for bicoid mRNA's regulated stability, fusions between bicoid and genes producing stable mRNAs were introduced into the Drosophila germ line by P-element-mediated transformation. The analysis of the fusion mRNAs identified a bicoid instability element (BIE) contained within a 43-nucleotide sequence immediately following the stop codon. The BIE is sufficient to destabilize the otherwise-stable ribosomal protein A1 mRNA and is separable from the previously identified bicoid mRNA localization signals and from the "nanos response element." Similar mechanisms may regulate a class of developmentally important maternal genes whose mRNA has a temporal profile similar to that of bicoid.

Formation of thebicoidmorphogen gradient: an mRNA gradient dictates the protein gradient

“…3H,I). Before nuclear cycle 14, bcd mRNA must be stable because little, if any, degradation was apparent, as previously observed in activated unfertilized eggs (Surdej and Jacobs-Lorena, 1998). …”

“…Therefore, bcd mRNA is degraded in the basal and apical periplasm, or only in the latter. This degradation is presumably mediated by a bcd instability element (BIE) located within a 43-nucleotide sequence following the stop codon (Surdej and Jacobs-Lorena, 1998). In mammals, Stau may trigger the degradation of an mRNA by binding to its 3ЈUTR and to the nonsense-mediated decay (NMD) factor Upf1, in a process that is different from NMD and is called Staufenmediated mRNA decay (SMD) (Kim et al, 2005).…”

Stage-Specific Expression and Targeting of Cyst Wall Protein–Green Fluorescent Protein Chimeras inGiardia

“…A possible contribution of the 11 nt 5ЈUTR, which was the only other CWP1-derived sequence in the mRNA tested, will have to be examined. Modulation of mRNA stability via cis motifs in the 3ЈUTR appears to be ubiquitous in cells that undergo differentiation and has been described in protozoa (Vanhamme and Pays, 1995), Drosophila (Surdej and Jacobs-Lorena, 1998), mammals (Mitchusson et al, 1998), and other organisms. Particularly in protozoa, the sequence motifs responsible for interaction with putative trans-acting factors that influence mRNA instability have been difficult to pin down, because multiple and sometimes widely spaced regions are involved and consensus motifs are very degenerate Schurch et al, 1997;Wilson et al, 1999).…”

The maternal-to-zygotic transition: a play in two acts

“…bcd) degradation pathways; and those targeted by both (e.g. Hsp83) (Bashirullah et al, 1999;Surdej and Jacobs-Lorena, 1998). (B) In the mouse, genomic profiling (Hamatani et al, 2004) has revealed clusters of maternal transcripts that appear to degrade with kinetics that correspond to the subsets identified in D. melanogaster: Clusters 3 and 9 degrade in the absence of significant zygotic transcription; degradation of cluster 7 transcripts appears to accelerate coincident with the onset of the major zygotic genome activation (ZGA) wave, whereas cluster 6b transcripts most resemble the stable subset.…”