DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1, a key regulator of the oocyte-to-embryo transition in C. elegans.
Oocyte maturation and fertilization initiates a dynamic and tightly regulated process in which a non-dividing oocyte is transformed into a rapidly dividing embryo. We have shown previously that two C. elegans CCCH zinc finger proteins, OMA-1 and OMA-2, have an essential and redundant function in oocyte maturation. Both OMA-1 and OMA-2 are expressed only in oocytes and 1-cell embryos, and need to be degraded rapidly after the first mitotic division for embryogenesis to proceed normally. We report here a distinct redundant function for OMA-1 and OMA-2 in the 1-cell embryo. Depletion of both oma-1 and oma-2 in embryos leads to embryonic lethality. We also show that OMA-1 protein is directly phosphorylated at T239 by the DYRK kinase MBK-2, and that phosphorylation at T239 is required both for OMA-1 function in the 1-cell embryo and its degradation after the first mitosis. OMA-1 phosphorylated at T239 is only detected within a short developmental window of 1-cell embryos, beginning soon after the proposed activation of MBK-2. Phosphorylation at T239 facilitates subsequent phosphorylation of OMA-1 by another kinase, GSK-3, at T339 in vitro. Phosphorylation at both T239 and T339 are essential for correctly-timed OMA-1 degradation in vivo. We propose that a series of precisely-timed phosphorylation events regulates both the activity and the timing of degradation for OMA proteins, thereby allowing restricted and distinct functions of OMA-1 and OMA-2 in the maturing oocyte and 1-cell embryo, ensuring a normal oocyte-to-embryo transition in C. elegans.
Nishi
Yuichi
Y
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
Lin
Rueyling
R
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D000097603:Dyrk Kinases
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D038362:Glycogen Synthase Kinase 3; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D014443:Tyrosine; D000097603:Dyrk Kinases; C440205:OMA-1 protein, C elegans; C473076:oma-2 protein, C elegans; C478059:MBK-2 protein, C elegans