COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in C. elegans germline stem cells

Abstract

AbstractRNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance in Caenorhabditis elegans and regulate the dynamics of progenitor cell proliferation and differentiation. The mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5, a component of the COP9 (constitutive photomorphogenesis 9) signalosome. Here, we find that the MPN (Mpr1/Pad1 N-terminal) metalloprotease domain of CSN-5 interacts with the PUF RNA-binding domain of FBFs and the interaction is conserved for human homologs hPUM1 and hCSN5. This interaction likely takes place outside of the COP9 holoenzyme. csn-5 mutation results in destabilization of FBF proteins in germline stem cells leading to phenotypes consistent with a partial FBF loss of function. We propose that a COP9-independent role of CSN-5 in the PUF protein stability and function may be conserved across species, with implications for human stem cell biology and cancer.Summary statementCSN-5 directly interacts with and stabilizes FBF-1/2 proteins, independently of CSN-5’s function in the COP9 complex, thereby promoting stem cell maintenance and oogenesis in C. elegans.