Oocyte and embryonic development depend crucially on correctly regulated translation of messenger RNAs (mRNAs) that are synthesized and stored by growing oocytes. But the underlying regulatory circuits remain largely unknown. We have discovered that growing oocytes (which are termed immature) accumulate mRNA encoding a protein termed the stem-loop-binding protein (SLBP). Slbp mRNA is translationally repressed at this stage, however, so only a small amount of SLBP protein is produced. During the final stage of oocyte development (termed maturation), Slbp becomes translationally activated. We have also found that the SLBP produced by both immature and maturing oocytes is essential for embryonic development. Our goals are to identify the mechanisms that regulate Slbp translation in oocytes and to determine the function of this translational control.
Objectives:
1. Identify the mechanism that regulates Slbp translation in immature oocytes.
2. Identify the mechanism that regulates Slbp translation in maturing oocytes.
3. Determine the developmental function of regulated Slbp translation.
We will determine whether Slbp mRNA in immature oocytes is localized in newly identified cytoplasmic structures, termed P-bodies, and whether disrupting these structures reverses its translational repression. Based on new results showing that a protein inhibitor must be degraded to permit Slbp translation in maturing oocytes, we will identify the sequence in Slbp that mediates the activity of the inhibitor and the protein that binds to this sequence. We will then create transgenic mice whose oocytes express a mutant Slbp that is translationally active in immature oocytes and test whether oocyte or embryonic development is disrupted.
Investigator: Hugh Clarke, PhD profile