SMAUG Is a Major Regulator of Maternal mRNA Destabilization in Drosophila and Its Translation Is Activated by the PAN GU Kinase

Abstract

In animals, egg activation triggers a cascade of posttranscriptional events that act on maternally synthesized RNAs. We show that, in Drosophila, the PAN GU (PNG) kinase sits near the top of this cascade, triggering translation of SMAUG (SMG), a multifunctional posttranscriptional regulator conserved from yeast to humans. Although PNG is required for cytoplasmic polyadenylation of smg mRNA, it regulates translation via mechanisms that are independent of its effects on the poly(A) tail. Analyses of mutants suggest that PNG relieves translational repression by PUMILIO (PUM) and one or more additional factors, which act in parallel through the smg mRNA's 3' untranslated region (UTR). Microarray-based gene expression profiling shows that SMG is a major regulator of maternal transcript destabilization. SMG-dependent mRNAs are enriched for gene ontology annotations for function in the cell cycle, suggesting a possible causal relationship between failure to eliminate these transcripts and the cell cycle defects in smg mutants.

Transitioning from egg to embryo: Triggers and mechanisms of egg activation

“…For instance, upon egg activation in Drosophila, the Pan Gu kinase stimulates smg and cyclinB mRNA polyadenylation and translation. In pan gu mutant embryos, overexpression of poly(A) polymerase rescues smg and cyclin B polyadenylation defects, but is not sufficient to induce their translation (Tadros et al, 2007;Vardy and Orr-Weaver, 2007).…”

“…3). Mature oocytes contain a remarkable array of mRNAs, representing 20 -45% of the genes in the mouse genome and 55% of the genes in the Drosophila genome (Wang et al, 2004;Evsikov et al, 2006;Tadros et al, 2007).…”

“…Six of these proteins are involved in patterning the early embryo and directing morphogenesis (including Bicoid, Torso, Toll, Nanos, Hunchback, and Caudal; Driever and Nusslein-Volhard, 1988;Casanova and Struhl, 1989;Tautz and Pfeifle, 1989;Gay and Keith, 1992;Wang et al, 1994;Dubnau and Struhl, 1996). The remaining two proteins known to be translated upon egg activation in Drosophila are Smaug (Smg), which plays a major role in the degradation of maternal transcripts (see below; Dahanukar et al, 1999;Tadros et al, 2007) and the Cdc25 homolog String, which activates MPF and is thus important for the rapid nuclear divisions that occur during early embryogenesis (Spradling, 1993). In Xenopus, maternally encoded proteins are similarly necessary for establishment of the embryonic axis and rapid early cell divisions (reviewed in .…”

“…Upon activation nanos mRNA is degraded everywhere except the posterior pole of the oocyte, where it is translated and functions in posterior patterning (Bashirullah et al, 1999;Bergsten and Gavis, 1999). Degradation can also remove mRNAs whose products are no longer needed or that interfere with later development, such as during the maternal to zygotic transition (MZT; mammals, zebrafish) or mid-blastula transition (MBT; Xenopus, Drosophila) (Bashirullah et al, 1999;Hamatani et al, 2004;Giraldez et al, 2006;Tadros et al, 2007).…”

“…3A; Tadros et al, 2007). The Smg protein has recently been identified as a major regulator of this process.…”