Scaffold attachment factor B (SAFB) proteins are evolutionarily conserved DNA/RNA binding proteins that are involved in multiple processes of gene expression. These proteins are broadly expressed with particular high expression observed in the nervous system. However, their physiological roles in neurons are largely unclear. Here we show that PHM-2, the sole SAFB ortholog in C. elegans, regulates synaptic transmission at the neuromuscular junctions through an effect on SLO-2 potassium channel. We found that phm-2 mutants suppress a sluggish phenotype of worms expressing a hyperactive SLO-2 channel, greatly reduces SLO-2-mediated neuronal whole-cell currents, and enhances neuromuscular synaptic transmission. In addition, we found that PHM-2 genetically interacts with another DNA/RNA binding protein, HRPU-2/hnRNP U, to control SLO-2 expression through a posttranscriptional mechanism. These results reveal a novel function of a SAFB protein in regulating neuronal activity, and may help understand the physiological roles of SAFB proteins in the nervous system of other species.
Copyright: © 2026 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.