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

Brian H. Carrick; Sarah L. Crittenden; MaryGrace Linsley; Stephany J. Costa Dos Santos; Marvin Wickens; Judith Kimble

doi:10.1261/rna.080307.124

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

Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

Corresponding authors: bcarrick{at}mrc-lmb.cam.ac.uk, jekimble{at}wisc.edu

Handling editor: Fatima Gebauer

↵1 Present address: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
↵2 Present address: Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA
↵3 Present address: WiCell Research Institute, Inc., Madison, WI 53719, USA

Abstract

Like all canonical PUF proteins, Caenorhabditis elegans FBF-2 binds to specific RNAs via tripartite recognition motifs. 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 the 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 the activity of an RNA-binding protein.

Keywords

Footnotes

Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.080307.124.
Freely available online through the RNA Open Access option.

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/.