title: MAPK regulation of maternal and zygotic Notch transcript stability in early development.
abstract: Spatiotemporal modulation of the evolutionarily conserved, intercellular Notch signaling pathway is important in the development of many animals. Examples include the regulation of neural-epidermal fate decisions in neurogenic ectoderm of Drosophila and somitogenesis in vertebrate presomitic mesoderm. In both these and most other cases, it appears that Notch-class transmembrane receptors are ubiquitously expressed. Modulation of the pathway is achieved primarily by the localized expression of the activating ligand or by alteration of receptor specificity through a glycosyl transferase. In contrast, we present this report of an instance where the abundance of the Notch-class mRNA itself is dynamically regulated. Taking advantage of the long cell cycle of the two-cell-stage embryo of the leech Helobdella robusta, we show that this regulation is achieved at the levels of both transcript stability and transcription. Moreover, MAPK signaling plays a significant role in regulating accumulation of the transcript by virtue of its effect on Hro-notch mRNA stability. Intracellular injection of heterologous reporter mRNAs shows that the Hro-notch 3' UTR, containing seven AU-rich elements, is key to regulating transcript stability. Thus, we show that regulation of the Notch pathway can occur at a previously underappreciated level, namely that of transcript stability. Given that AU-rich elements occur in the 3' UTR of Notch-class genes in Drosophila, human, and Caenorhabditis elegans, regulation of Notch signaling by modulation of mRNA levels may be operating in other animals as well.
authors.affiliation: Department of Molecular and Cell Biology, 385 LSA, University of California, Berkeley, CA 94720-3200, USA.
authors.forename: Foster C
authors.initials: FC
authors.lastname: Gonsalves
authors.forename: David A
authors.initials: DA
authors.lastname: Weisblat
mesh_terms: D000818:Animals; D001483:Base Sequence; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007865:Leeches / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics*; D014158:Transcription, Genetic; D015053:Zygote / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051880:Receptors, Notch; D048051:p38 Mitogen-Activated Protein Kinases