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

Emily Osterli, Mary Ellenbecker, Xiaobo Wang, Mikaya Terzo, Ketch Jacobson, De Anna Cuello, Ekaterina Voronina

Research output: Contribution to journalArticlepeer-review

Abstract

RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance and the sperm/oocyte switch in Caenorhabditis elegans, although the mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5), a component of the constitutive photomorphogenesis 9 (COP9) signalosome best known for its role in regulating protein degradation. Here, we find that the Mpr1/Pad1 N-terminal metalloprotease domain of CSN-5 interacts with the Pumilio and FBF RNA-binding domain of FBFs and the interaction is conserved for human homologs CSN5 and PUM1. The interaction between FBF-2 and CSN-5 can be detected in vivo by proximity ligation. csn-5 mutation results in the destabilization of FBF proteins, which may explain previously observed decrease in the numbers of germline stem and progenitor cells, and disruption of oogenesis. The loss of csn-5 does not decrease the levels of a related PUF protein PUF-3, and csn-5(lf) phenotype is not enhanced by fbf-1/2 knockdown, suggesting that the effect is specific to FBFs. The effect of csn-5 on oogenesis is largely independent of the COP9 signalosome and is cell autonomous. Surprisingly, the regulation of FBF protein levels involves a combination of COP9-dependent and COP9-independent mechanisms differentially affecting FBF-1 and FBF-2. This work supports a previously unappreciated role for CSN-5 in the stabilization of germline stem cell regulatory proteins FBF-1 and FBF-2.

Original languageEnglish
Article numberiyae033
JournalGenetics
Volume227
Issue number1
DOIs
StatePublished - May 2024

Keywords

  • COP9 signalosome
  • COPS5
  • CSN-2
  • CSN-6
  • PUM1
  • germline
  • oocyte development
  • COP9 Signalosome Complex/metabolism
  • Stem Cells/metabolism
  • RNA-Binding Proteins/metabolism
  • Animals
  • Caenorhabditis elegans/genetics
  • Protein Stability
  • Caenorhabditis elegans Proteins/metabolism
  • Oogenesis/genetics
  • Germ Cells/metabolism

Fingerprint

Dive into the research topics of 'COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells'. Together they form a unique fingerprint.

Cite this