Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two tra...

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Published in:Journal of cell science
Main Authors: Huggins, Hayden P, Subash, Jacob S, Stoffel, Hamilton, Henderson, Melissa A, Hoffman, Jenna L, Buckner, David S, Sengupta, Madhu S, Boag, Peter R, Lee, Myon-Hee, Keiper, Brett D
Format: Journal Article
Language:English
Published: England 01-01-2020
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Abstract Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1 and -3) that bind m7GTP mRNA caps during C. elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline, localizes to germ granules but distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression of IFE-1 in spermatocytes, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization, and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.
AbstractList Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1 and -3) that bind m7GTP mRNA caps during C. elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline, localizes to germ granules but distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression of IFE-1 in spermatocytes, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization, and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.
Author Subash, Jacob S
Buckner, David S
Henderson, Melissa A
Lee, Myon-Hee
Keiper, Brett D
Stoffel, Hamilton
Sengupta, Madhu S
Hoffman, Jenna L
Boag, Peter R
Huggins, Hayden P
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  surname: Huggins
  fullname: Huggins, Hayden P
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: Jacob S
  surname: Subash
  fullname: Subash, Jacob S
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: Hamilton
  surname: Stoffel
  fullname: Stoffel, Hamilton
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: Melissa A
  surname: Henderson
  fullname: Henderson, Melissa A
  organization: Department of Molecular Sciences, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN 37752, USA
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  givenname: Jenna L
  surname: Hoffman
  fullname: Hoffman, Jenna L
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: David S
  surname: Buckner
  fullname: Buckner, David S
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: Madhu S
  surname: Sengupta
  fullname: Sengupta, Madhu S
  organization: Monash Biomedicine Discovery Institute and Department of Biochemistry & Molecular Biology, Monash University, Melbourne, Australia
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  givenname: Peter R
  orcidid: 0000-0002-0889-0859
  surname: Boag
  fullname: Boag, Peter R
  organization: Monash Biomedicine Discovery Institute and Department of Biochemistry & Molecular Biology, Monash University, Melbourne, Australia
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  givenname: Myon-Hee
  orcidid: 0000-0001-9020-2391
  surname: Lee
  fullname: Lee, Myon-Hee
  organization: Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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  givenname: Brett D
  orcidid: 0000-0002-8621-9825
  surname: Keiper
  fullname: Keiper, Brett D
  organization: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
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Keywords eIF4E
Germline sex determination
Polyribosomes/polysomes
Gametogenesis
4EBP
mRNA translational control
Language English
License 2020. Published by The Company of Biologists Ltd.
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Snippet Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA...
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