Meiotic cell cycle progression during vertebrate oocyte maturation is controlled by proteins that are translated from maternally derived mRNAs. In the model system, Xenopus laevis, translational induction of dormant mRNAs encoding cell cycle control proteins must occur in a strict temporal order. The induction of maternal mRNA translation is directed through regulatory elements in the mRNA 3' untranslated regions (3' UTRs). In this study, we identify and characterize a novel regulatory element in the Weel 3' UTR. This novel element was characterized and termed a translation control sequence (TCS). The TCS was shown to mediate repression in immature oocytes and early translational activation in response to progesterone. The consensus TCS is present in 12.3% of the non-redundant Xenopus mRNA 3' UTR entries (1159 mRNAs) and a very similar percentage was found in mammalian mRNAs 3'UTRs, suggesting that TCS-dependent mRNA translational control may be evolutionarily conserved. We began characterization of TCS regulation by identification of a novel TCS-specific binding protein, Zygotic arrest 2 (Zar2). Zar2 appears to be conserved in all vertebrate species. We demonstrated that the sequence-specific RNA binding activity of Zar2 required an atypical plant homeodomain (PHD). We further addressed the issue of how multiple distinct regulatory pathways are integrated and coordinated during oocyte maturation. We determined the epistasis of Ringo, TCS, Musashi and CPE function in response to progesterone stimulation. Our findings indicate that early Musashi and TCS pathways function in parallel and are downstream of Ringo. Taken together, this study provides a novel insight into the complexity of 3'UTR-directed mRNA translational regulation and establishes a framework for understanding how distinct pathways are functionally integrated to exert defied patterns of temporal control during meiotic cell cycle progression.
|School:||University of Arkansas for Medical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 69/12, Dissertation Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Physiology|
|Keywords:||Cell cycle, Oocytes, Translation control sequence, mRNA|
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