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-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.
Original language | English |
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Pages (from-to) | 1380-1390 |
Number of pages | 11 |
Journal | Cell Reports |
Volume | 8 |
Issue number | 5 |
DOIs | |
State | Published - 2014 |
Externally published | Yes |
Bibliographical note
Funding 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.
Publisher Copyright:
© 2014 The Authors.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)