Alternative 3′ UTR Selection Controls PAR-5 Homeostasis and Cell Polarity in C. elegans Embryos

Abstract

Cell polarity in one-cell C. elegans embryos guides asymmetric cell division and cell-fate specification. Shortly after fertilization, embryos establish two antagonistic cortical domains of PAR proteins. Here, we find that the conserved polarity factor PAR-5 regulates PAR domain size in a dose-dependent manner. Using quantitative imaging and controlled genetic manipulation, we find that PAR-5 protein levels reflect the cumulative output of three mRNA isoforms with different translational efficiencies mediated by their 3′ UTRs. 3′ UTR selection is regulated, influencing PAR-5 protein abundance. Alternative splicing underlies the selection of par-5 3′ UTR isoforms. 3′ UTR splicing is enhanced by the SR protein kinase SPK-1, and accordingly, SPK-1 is required for wild-type PAR-5 levels and PAR domain size. Precise regulation of par-5 isoform selection is essential for polarization when the posterior PAR network is compromised. Together, strict control of PAR-5 protein levels and feedback from polarity to par-5 3′ UTR selection confer robustness to embryo polarization.