Journal Article

Multiple Mechanisms Inactivate the LIN-41 RNA-Binding Protein To Ensure a Robust Oocyte-to-Embryo Transition in Caenorhabditis elegans

Greenstein, David, Huelgas-Morales, Gabriela, Tsukamoto, Tatsuya, Spike, Caroline A

2018

Overview

In the nematode Caenorhabditis elegans, the conserved LIN-41 RNA-binding protein is a translational repressor that coordinately controls oocyte growth and meiotic maturation. LIN-41 exerts these effects, at least in part, by preventing the premature activation of the cyclin-dependent kinase CDK-1. Here we investigate the mechanism by which LIN-41 is rapidly eliminated upon the onset of meiotic maturation. Elimination of LIN-41 requires the activities of CDK-1 and multiple SCF (Skp1, Cul1, and F-box protein)-type E3 ubiquitin ligase subunits, including the conserved substrate adaptor protein SEL-10/Fbw7/Cdc4, suggesting that LIN-41 is a target of ubiquitin-mediated protein degradation. Within the LIN-41 protein, two nonoverlapping regions, Deg-A and Deg-B, are individually necessary for LIN-41 degradation; both contain several potential phosphodegron sequences, and at least one of these sequences is required for LIN-41 degradation. Finally, Deg-A and Deg-B are sufficient, in combination, to mediate SEL-10-dependent degradation when transplanted into a different oocyte protein. Although LIN-41 is a potent inhibitor of protein translation and M phase entry, the failure to eliminate LIN-41 from early embryos does not result in the continued translational repression of LIN-41 oocyte messenger RNA targets. Based on these observations, we propose a model for the elimination of LIN-41 by the SEL-10 E3 ubiquitin ligase and suggest that LIN-41 is inactivated before it is degraded. Furthermore, we provide evidence that another RNA-binding protein, the GLD-1 tumor suppressor, is regulated similarly. Redundant mechanisms to extinguish translational repression by RNA-binding proteins may both control and provide robustness to irreversible developmental transitions, including meiotic maturation and the oocyte-to-embryo transition.

• Publisher: Genetics Society of America
• Subject: Amino Acid Sequence / Animals / Biodegradation / Caenorhabditis elegans / Caenorhabditis elegans - cytology / Caenorhabditis elegans - embryology / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - chemistry / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Cdc4 protein / Cell cycle / Cell division / Cyclin-dependent kinase / Cyclin-dependent kinases / Embryo, Nonmammalian - metabolism / Embryos / F-box protein / Female / Gene Editing / Gene Expression Regulation, Developmental / Genetics / Investigations / Kinases / Maturation / Meiosis / mRNA / Nematodes / Oocytes - metabolism / Phenotype / Phosphorylation / Protein Domains / Proteins / Proteolysis / Regulation / Ribonucleic acid / RNA / RNA-binding protein / Robust control / Sperm / Substrates / Transcription Factors - chemistry / Transcription Factors - genetics / Transcription Factors - metabolism / Translation / Tumor suppressor genes / Ubiquitin / Ubiquitin-protein ligase / Worms