title: 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.
authors.affiliation: Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria. Electronic address: mmikl@gmx.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Mikl
authors.affiliation: Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria. Electronic address: cowan@imp.ac.at.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Cowan
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D059368:RNA Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D059368:RNA Isoforms; D012333:RNA, Messenger; C087977:par-2 protein, C elegans; C106207:par-5 protein, C elegans; C574427:SPK-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases