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

  1. Judith Kimble2
  1. 1 MRC Laboratory of Molecular Biology;
  2. 2 University of Wisconsin-Madison;
  3. 3 University of Washington;
  4. 4 WiCell Research Institute, Inc.
  1. * Corresponding author; email: bcarrick{at}mrc-lmb.cam.ac.uk

Abstract

Like all canonical PUF proteins, C. elegans FBF-2 binds to specific RNAs via tripartite recognition motifs (TRMs). Here we report that an FBF-2 mutant protein that cannot bind to RNA, is nonetheless biologically active and maintains stem cells. This unexpected result challenges the conventional wisdom that RBPs must bind to RNAs to achieve biological activity. Also unexpectedly, FBF-2 interactions with partner proteins can compensate for loss of RNA-binding. FBF-2 only loses biological activity when its RNA-binding and partner interactions are both defective. These findings highlight the complementary contributions of RNA-binding and protein partner interactions to activity of an RNA-binding protein.

Keywords

  • Received October 30, 2024.
  • Accepted January 31, 2025.

This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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  1. RNA rna.080307.124 Published by Cold Spring Harbor Laboratory Press for the RNA Society

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