The APC/CFZY–1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans

Abstract

During oocyte maturation and the oocyte-to-embryo transition, key developmental regulators such as RNA-binding proteins coordinate translation of particular messenger RNA (mRNAs) and related developmental processes by binding to their cognate maternal mRNAs. In the nematode Caenorhabditis elegans, these processes are regulated by a set of CCCH zinc finger proteins. Oocyte maturation defective-1 (OMA-1) and OMA-2 are two functionally redundant CCCH zinc finger proteins that turnover rapidly during the first embryonic cell division. These turnovers are required for proper transition from oogenesis to embryogenesis. A gain-of-function mutant of OMA-1, oma-1(zu405), stabilizes and delays degradation of OMA-1, resulting in delayed turnover and mis-segregation of other cell fate determinants, which eventually causes embryonic lethality. We performed a large-scale forward genetic screen to identify suppressors of the oma-1(zu405) mutant. We show here that multiple alleles affecting functions of various anaphase promoting complex/cyclosome (APC/C) subunits, including MAT-1, MAT-2, MAT-3, EMB-30, and FZY-1, suppress the gain-of-function mutant of OMA-1. Transcriptome analysis suggested that overall transcription in early embryos occurred after introducing mutations in APC/C genes into the oma-1(zu405) mutant. Mutations in APC/C genes prevent OMA-1 enrichment in P granules and correct delayed degradation of downstream cell fate determinants including pharynx and intestine in excess-1 (PIE-1), posterior segregation-1 (POS-1), muscle excess-3 (MEX-3), and maternal effect germ-cell defective-1 (MEG-1). We demonstrated that only the activator FZY-1, but not FZR-1, is incorporated in the APC/C complex to regulate the oocyte-to-embryo transition. Our findings suggested a genetic relationship linking the APC/C complex and OMA-1, and support a model in which the APC/C complex promotes P granule accumulation and modifies RNA binding of OMA-1 to regulate the oocyte-to-embryo transition process.

Live-organismal Transcriptomics

“…11c,d), strongly suggesting that the zygotic expression level of fzy-1 is the core determinant of organimal fates. Consistently, a recent study showed that fzy-1 serves as a suppressor of embryonic lethality in the oma-1 zu405 , 24 supporting the notion that the zygotic expression level of fzy-1 is the core determinant of the apparently stochastic life-or-death fate in oma-1 zu405 .…”

“…23 Past findings suggested the existence of the upstream determinant leading to lethal mistransformation of the cell fate in the eightcell stage oma-1 zu405 embryos. 24 To explore the initial determinant of fates, we subjected embryos to five repeated RNA samplings from five cell types (zygote, anterior cells in the two-and four-cell stages named AB and ABa, and posterior cells in the two-and four-cell stages named P1 and P2) and performed subcellular RNA-seq for live-organism transcriptomics by optimising eggshell removal conditions (Supplementary Figs. 8a-8c) and voltage applications (Supplementary Fig.…”

Identification, characterization and expression profiles of E2 and E3 gene superfamilies during the development of tetrasporophytes in Gracilariopsis lemaneiformis (Rhodophyta)

“…Ten of 51 genes encoded E3 ubiquitin ligases (UPL3, APC2, APC1, APC8, APC3, RBX1, COP1, FANCL, HRD1 and LUL3). Two others, CDC20 and CDH1 (CDC20 homologue 1) were activators of the APC/C complex [ 78 , 79 ]. We mapped the APC/C and its activator genes to the Arabidopsis thaliana genome to understand their possible functions.…”

Preimplantation embryo gene expression: 56 years of discovery, and counting

“…Significant insights into the temporal regulation of maternal proteins have come from studies in Caenorhabditis elegans , in which a DYRK family kinase member (MBK‐2) coordinates maternal protein degradation including the oocyte P‐granule component and translational repressor, OMA1 (Pellettieri et al, 2003; Robertson & Lin, 2015). OMA function is positively regulated by the APC/C complex, potentially via another intermediate regulator (Hu, Hu, et al, 2021). In another interesting pathway, the cullin system CUL‐2 promotes degradation of MEME1 to allow correct meiotic progression after fertilization (Ataeian et al, 2016).…”