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The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA.

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The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA.

Brian H Carrick1,2, Sarah L Crittenden1, MaryGrace Linsley1,3

  • 1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI.

Biorxiv : the Preprint Server for Biology
|November 1, 2024
PubMed
Summary

RNA-binding protein FBF-2 in C. elegans maintains stem cells even without RNA binding. Protein interactions can compensate for lost RNA-binding, challenging established RBP activity models.

Keywords:
C. elegansPUF RNA binding proteinPUF partnershipsgermline stem cellssperm/oocyte cell fate decision

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • PUF proteins, including C. elegans FBF-2, are known to bind specific RNAs via tripartite recognition motifs (TRMs).
  • The conventional understanding is that RNA-binding is essential for the biological activity of RNA-binding proteins (RBPs).

Purpose of the Study:

  • To investigate the role of RNA-binding in the biological activity of FBF-2.
  • To determine if protein-protein interactions can influence FBF-2 activity independently of RNA binding.

Main Methods:

  • Generation and analysis of an FBF-2 mutant protein incapable of RNA binding.
  • Assessment of the biological activity of the mutant FBF-2 in maintaining stem cells in C. elegans.
  • Evaluation of FBF-2 interactions with partner proteins.

Main Results:

  • An FBF-2 mutant lacking RNA-binding capability remained biologically active and successfully maintained stem cells.
  • FBF-2's biological activity was preserved when its interactions with partner proteins compensated for the loss of RNA-binding.
  • Complete loss of biological activity occurred only when both RNA-binding and partner protein interactions were compromised.

Conclusions:

  • RNA binding is not strictly essential for the biological activity of all RBPs, challenging existing paradigms.
  • Protein-protein interactions can functionally substitute for RNA-binding in RBPs like FBF-2.
  • The activity of RBPs is modulated by a combination of RNA-binding and protein partner interactions.