POS-1 Promotes Endo-mesoderm Development by Inhibiting the Cytoplasmic Polyadenylation of neg-1 mRNA
Program in Molecular Medicine; RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Carrier Proteins; Cell Differentiation; Cytoplasm; Gene Expression Regulation, Developmental; Germ Cells; Mesoderm; Nuclear Proteins; Polyadenylation; RNA, Helminth; RNA, Messenger
Cell Biology | Developmental Biology | Molecular Biology
The regulation of mRNA translation is of fundamental importance in biological mechanisms ranging from embryonic axis specification to the formation of long-term memory. POS-1 is one of several CCCH zinc-finger RNA-binding proteins that regulate cell fate specification during C. elegans embryogenesis. Paradoxically, pos-1 mutants exhibit striking defects in endo-mesoderm development but have wild-type distributions of SKN-1, a key determinant of endo-mesoderm fates. RNAi screens for pos-1 suppressors identified genes encoding the cytoplasmic poly(A)-polymerase homolog GLD-2, the Bicaudal-C homolog GLD-3, and the protein NEG-1. We show that NEG-1 localizes in anterior nuclei, where it negatively regulates endo-mesoderm fates. In posterior cells, POS-1 binds the neg-1 3' UTR to oppose GLD-2 and GLD-3 activities that promote NEG-1 expression and cytoplasmic lengthening of the neg-1 mRNA poly(A) tail. Our findings uncover an intricate series of post-transcriptional regulatory interactions that, together, achieve precise spatial expression of endo-mesoderm fates in C. elegans embryos.
DOI of Published Version
Dev Cell. 2015 Jul 6;34(1):108-18. doi: 10.1016/j.devcel.2015.05.024. Epub 2015 Jun 18. Link to article on publisher's site
Elewa, Ahmed M.; Shirayama, Masaki; Kaymak, Ebru; Harrison, Paul F.; Powell, David R.; Du, Zhuo; Chute, Christopher D.; Woolf, Hannah; Yi, Dongni; Ishidate, Takao; Srinivasan, Jagan; Bao, Zhirong; Beilharz, Traude H.; Ryder, Sean P.; and Mello, Craig C., "POS-1 Promotes Endo-mesoderm Development by Inhibiting the Cytoplasmic Polyadenylation of neg-1 mRNA" (2015). Program in Molecular Medicine Publications and Presentations. 58.