Bicaudal-C (Bic-C) encodes a KH-type RNA binding protein required maternally for anterior patterning of the Drosophila oocyte and correct migration of the centripetal follicle cells. In Drosophila, premature translation of the germ-plasm determinant Oskar in Bic-C mutant oocytes suggests a function for Bic-C in post-transcriptional gene regulation. / Purification and microarray analysis of Bic-C containing ribonucleoprotein complexes revealed that Bic-C associates with multiple transcripts encoding functionally-related components of the Wnt/Frizzled/Dishevelled signaling pathway that regulate actin dynamics, in addition to its own mRNA. Using transgenic reporter constructs, Bic-C was demonstrated to destabilize its own mRNA via cis-acting 5' UTR elements. When auto-regulation was bypassed and Bic-C was over-expressed in the female germline, premature cytoplasmic streaming was induced, disrupting axial patterning through displacement of both Gurken (Grk) and oskar. These phenotypes can also be induced by disruption of the actin cytoskeleton with pharmacological agents and are similar to those described for hypomorphic mutant alleles of orb, which encodes a CPEB-like protein that promotes polyadenylation of target mRNAs. The Bic-C overexpression phenotypes require its RNA binding activity, are substantially enhanced by mutations affecting orb and poly(A) polymerase, and are suppressed by mutations affecting the deadenylase CCR4 and its accessory protein NOT3. Co-immunoprecipitation experiments demonstrate that Bic-C associates with components of the deadenylase complex and with components of an ER-associated RNP complex that includes Me31B, PABP and Trailer-hitch. The latter complex is involved in Grk exocytosis. Accordingly, Grk secretion is defective in Bic-C mutants. / Taken together, these results support a model whereby Bic-C antagonizes Orb function by negatively regulating the expression of Orb target mRNAs, through recruitment of the deadenylase machinery, that are involved in coordinating cytoplasmic movements. Furthermore, this work identifies a novel function of Bic-C in dorsal/ventral patterning by promoting Grk secretion.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.102968 |
| Date | January 2006 |
| Creators | Chicoine, Jarred. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biology.) |
| Rights | © Jarred Chicoine, 2006 |
| Relation | alephsysno: 002614326, proquestno: AAINR32165, Theses scanned by UMI/ProQuest. |
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