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 AM, Shirayama M, Kaymak E, Harrison PF, Powell DR, Du Z, Chute CD, Woolf H, Yi D, Ishidate T, Srinivasan J, Bao Z, Beilharz TH, Ryder SP, Mello CC. (2015). POS-1 Promotes Endo-mesoderm Development by Inhibiting the Cytoplasmic Polyadenylation of neg-1 mRNA. Program in Molecular Medicine Publications. https://doi.org/10.1016/j.devcel.2015.05.024. Retrieved from https://escholarship.umassmed.edu/pmm_pp/58