Conserved regulation of MAP kinase expression by PUF RNA-binding proteins.

Myon Hee Lee, Brad Hook, Guangjin Pan, Aaron M. Kershner, Christopher Merritt, Geraldine Seydoux, James A. Thomson, Marvin Wickens, Judith Kimble

Research output: Contribution to journalArticle

Abstract

Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.

Original languageEnglish (US)
JournalPLoS Genetics
Volume3
Issue number12
DOIs
StatePublished - Dec 28 2007

Fingerprint

RNA-binding proteins
RNA-Binding Proteins
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
RNA
Phosphotransferases
protein
Caenorhabditis elegans
3' Untranslated Regions
Dual Specificity Phosphatase 1
3' untranslated regions
apoptosis
Apoptosis
stem cells
phosphatase
germ cells
Messenger RNA
embryonic stem cells
Mitogen-Activated Protein Kinase Phosphatases
stem

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. / Lee, Myon Hee; Hook, Brad; Pan, Guangjin; Kershner, Aaron M.; Merritt, Christopher; Seydoux, Geraldine; Thomson, James A.; Wickens, Marvin; Kimble, Judith.

In: PLoS Genetics, Vol. 3, No. 12, 28.12.2007.

Research output: Contribution to journalArticle

Lee, MH, Hook, B, Pan, G, Kershner, AM, Merritt, C, Seydoux, G, Thomson, JA, Wickens, M & Kimble, J 2007, 'Conserved regulation of MAP kinase expression by PUF RNA-binding proteins.', PLoS Genetics, vol. 3, no. 12. https://doi.org/10.1371/journal.pgen.0030233
Lee, Myon Hee ; Hook, Brad ; Pan, Guangjin ; Kershner, Aaron M. ; Merritt, Christopher ; Seydoux, Geraldine ; Thomson, James A. ; Wickens, Marvin ; Kimble, Judith. / Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. In: PLoS Genetics. 2007 ; Vol. 3, No. 12.
@article{18a07ee3dbe645b29b815358b92bd41a,
title = "Conserved regulation of MAP kinase expression by PUF RNA-binding proteins.",
abstract = "Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.",
author = "Lee, {Myon Hee} and Brad Hook and Guangjin Pan and Kershner, {Aaron M.} and Christopher Merritt and Geraldine Seydoux and Thomson, {James A.} and Marvin Wickens and Judith Kimble",
year = "2007",
month = "12",
day = "28",
doi = "10.1371/journal.pgen.0030233",
language = "English (US)",
volume = "3",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Conserved regulation of MAP kinase expression by PUF RNA-binding proteins.

AU - Lee, Myon Hee

AU - Hook, Brad

AU - Pan, Guangjin

AU - Kershner, Aaron M.

AU - Merritt, Christopher

AU - Seydoux, Geraldine

AU - Thomson, James A.

AU - Wickens, Marvin

AU - Kimble, Judith

PY - 2007/12/28

Y1 - 2007/12/28

N2 - Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.

AB - Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.

UR - http://www.scopus.com/inward/record.url?scp=39549111045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39549111045&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.0030233

DO - 10.1371/journal.pgen.0030233

M3 - Article

C2 - 18166083

AN - SCOPUS:37749015690

VL - 3

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 12

ER -