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

Myon-Hee Lee1, Brad Hook, Guangjin Pan

  • 1Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

Plos Genetics
|January 2, 2008
PubMed

Insights

PUF proteins directly regulate Mitogen-activated protein kinase (MAPK) mRNA levels in both worms and human stem cells. This conserved mechanism, alongside MAPK phosphatases, influences stem cell maintenance and tumor progression.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Stem Cell Biology

Background:

  • Mitogen-activated protein kinase (MAPK) and PUF RNA-binding proteins are crucial for development and tissue homeostasis.
  • PUF proteins regulate gene expression post-transcriptionally.

Purpose of the Study:

  • To investigate the direct role of PUF proteins in regulating MAPK mRNA expression.
  • To explore the conserved function of PUF-MAPK interaction in development and disease.

Main Methods:

  • RNA-binding assays (coprecipitation) in C. elegans.
  • Reporter assays in human embryonic stem cells.
  • Analysis of gene expression in wild-type and mutant organisms.

Main Results:

  • PUF proteins bind to the 3' UTR of MAPK/ERK-encoding mRNAs, downregulating their expression.
  • This repression is conserved from C. elegans to human cells.
  • In C. elegans, FBF acts with LIP-1 (MAPK phosphatase) to control MAPK activity, impacting germline stem cell self-renewal and apoptosis.

Conclusions:

  • PUF proteins are direct negative regulators of MAPK mRNA.
  • The PUF-MAPK regulatory axis is conserved across species.
  • Dual regulation of MAPK by PUF and MAPK phosphatases may be a conserved mechanism for stem cell maintenance and tumor suppression.

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