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

Martin Mikl; Carrie R. Cowan

doi:10.1016/j.celrep.2014.08.004

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

Martin Mikl, Carrie R. Cowan

Research output: Contribution to journal › Article › peer-review

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
Pages (from-to)	1380-1390
Number of pages	11
Journal	Cell Reports
Volume	8
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2014.08.004
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)

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10.1016/j.celrep.2014.08.004

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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-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.",

author = "Martin Mikl and Cowan, {Carrie R.}",

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: {\textcopyright} 2014 The Authors.",

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N2 - 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.

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

Abstract

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ASJC Scopus subject areas

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