Bipartite interaction sites differentially modulate RNA-binding affinity of a protein complex essential for germline stem cell self-renewal

Author:

Qiu Chen1,Wine Robert N1,Campbell Zachary T2ORCID,Hall Traci M Tanaka1ORCID

Affiliation:

1. Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA

2. Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75025, USA

Abstract

Abstract In C. elegans, PUF proteins promote germline stem cell self-renewal. Their functions hinge on partnerships with two proteins that are redundantly required for stem cell maintenance. Here we focus on understanding how the essential partner protein, LST-1, modulates mRNA regulation by the PUF protein, FBF-2. LST-1 contains two nonidentical sites of interaction with FBF-2, LST-1 A and B. Our crystal structures of complexes of FBF-2, LST-1 A, and RNA visualize how FBF-2 associates with LST-1 A versus LST-1 B. One commonality is that FBF-2 contacts the conserved lysine and leucine side chains in the KxxL motifs in LST-1 A and B. A key difference is that FBF-2 forms unique contacts with regions N- and C-terminal to the KxxL motif. Consequently, LST-1 A does not modulate the RNA-binding affinity of FBF-2, whereas LST-1 B decreases RNA-binding affinity of FBF-2. The N-terminal region of LST-1 B, which binds near the 5′ end of RNA elements, is essential to modulate FBF-2 RNA-binding affinity, while the C-terminal residues of LST-1 B contribute strong binding affinity to FBF-2. We conclude that LST-1 has the potential to impact which mRNAs are regulated depending on the precise nature of engagement through its functionally distinct FBF binding sites.

Funder

National Institutes of Health

National Institute of Environmental Health Sciences

Department of Energy

Publisher

Oxford University Press (OUP)

Subject

Genetics

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