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The 40S Ribosomal Protein uS5 (RPS2) Assembles Into an Extraribosomal Complex With Human ZNF277 That Competes With the PRMT3-uS5 Interaction

The 40S Ribosomal Protein uS5 (RPS2) Assembles Into an Extraribosomal Complex With Human ZNF277 That Competes With the PRMT3-uS5 Interaction

Kiersten L Dionne, Danny Bergeron, Anne-Marie Landry-Voyer, François Bachand

J Biol Chem. 2019 Feb 8;294(6):1944-1955.

PMID: 30530495

Abstract:

Ribosomal (r)-proteins are generally viewed as ubiquitous, constitutive proteins that simply function to maintain ribosome integrity. However, findings in the past decade have led to the idea that r-proteins have evolved specialized functions beyond the ribosome. For example, the 40S ribosomal protein uS5 (RPS2) is known to form an extraribosomal complex with the protein arginine methyltransferase PRMT3 that is conserved from fission yeast to humans. However, the full scope of uS5's extraribosomal functions, including whether uS5 interacts with any other proteins, is not known. In this study, we identify the conserved zinc finger protein 277 (ZNF277) as a new uS5-associated protein by using quantitative proteomics approaches in human cells. As previously shown for PRMT3, we found that ZNF277 uses a C2H2-type zinc finger domain to recognize uS5. Analysis of protein-protein interactions in living cells indicated that the ZNF277-uS5 complex is found in the cytoplasm and the nucleolus. Furthermore, we show that ZNF277 and PRMT3 compete for uS5 binding, because overexpression of PRMT3 inhibited the formation of the ZNF277-uS5 complex, whereas depletion of cellular ZNF277 resulted in increased levels of uS5-PRMT3. Notably, our results reveal that ZNF277 recognizes nascent uS5 in the course of mRNA translation, suggesting cotranslational assembly of the ZNF277-uS5 complex. Our findings thus unveil an intricate network of evolutionarily conserved protein-protein interactions involving extraribosomal uS5, suggesting a key role for uS5 beyond the ribosome.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416083	PRMT3 human			Price

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