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-dependentmanner. 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 isessential 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.
|Number of pages||11|
|State||Published - 2014|
Bibliographical noteFunding Information:
The authors thank Carsten Hoege, Anthony A. Hyman, Christian Eckmann (MPI-CBG), Nate Goehring (Cancer Research UK, London), and Geraldine Seydoux (Johns Hopkins University, Baltimore) for reagents; Juergen Knoblich, Javier Martinez, and Luisa Cochella for discussion and suggestions at various stages of the project; and Bartlomiej Gebarski and Harue Wada for technical assistance. Solexa sequencing was performed at the CSF NGS Unit ( http://www.csf.ac.at ). Some worm strains used in this study were provided by the Caenorhabditis Genetics Center, which is funded by the NIH. Research at the IMP is partially funded by Boehringer Ingelheim.
© 2014 The Authors.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)