Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation

Minakhina, Svetlana; Naryshkina, Tatyana; Changela, Neha; Tan, William; Steward, Ruth

doi:10.1371/journal.pone.0147631

Cited by 12 publications

(13 citation statements)

References 68 publications

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“…Mutually exclusive interactions of uS5 with ZNF277 and PRMT3 result in the formation of PDCD2-uS5-ZNF277 (lower left) and PDCD2L-uS5-ZNF277 (lower right) complexes. The existence of conserved complexes in Drosophila is supported by results from high-throughput two-hybrid screening and biochemical studies (28,30), showing that homologs of PRMT3 (Art3), ZNF277 (CG9890), PDCD2 (Zfrp8), and PDCD2L (Trus) interact with uS5 (Sop).…”

Section: Discussionmentioning

confidence: 98%

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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

Dionne

Bergeron

Landry-Voyer

et al. 2019

Journal of Biological Chemistry

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Edited by Karin Musier-ForsythRibosomal (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. . 2 The abbreviations used are: r-protein, ribosomal protein; ZNF277, zinc finger protein 277; PRMT3, protein arginine methyltransferase 3; uS5/RPS2, 40S ribosomal protein S2; ZF, zinc finger; SILAC, stable isotope labeling by amino acids in cell culture; PDCD2, programmed cell death protein 2; PDCD2L, PDCD2-like protein; AP, affinity purification; BiFC, bimolecular fluorescence complementation; YFP, yellow fluorescent protein; qPCR, quantitative PCR; MCS, multiple cloning site.

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Section: Discussionmentioning

confidence: 98%

“…Specifically, biochemical analysis revealed that PDCD2 and PDCD2L form distinct complexes with uS5-PRMT3, because PDCD2L was not detected in a PDCD2 purification, and reciprocally, PDCD2 was not identified as a PDCD2L-associated protein (29). Interestingly, the uS5-PDCD2 interaction has been also observed in Drosophila (30).…”

mentioning

confidence: 99%

The 40S ribosomal protein uS5 (RPS2) assembles into an extraribosomal complex with human ZNF277 that competes with the PRMT3–uS5 interaction

Dionne

Bergeron

Landry-Voyer

et al. 2019

Journal of Biological Chemistry

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“…Tsr4 is evolutionarily conserved among eukaryotes (30). PDCD2/Zfrp8 in Drosophila directly interacts with Rps2, is both cytoplasmic and nuclear, and appears to serve a function in 40S production, but the significance of its interaction with Rps2 has not been extensively characterized (29,41,49). Humans have two Tsr4 homologs, PDCD2 and PDCD2L (30), and expression of human PDCD2 can fully complement the loss of Drosophila PDCD2/Zfrp8, indicating functional conservation (49).…”

Section: How Does Tsr4 Facilitate Rps2 Expression?mentioning

confidence: 99%

Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rps2 in Saccharomyces cerevisiae

Black

Musalgaonkar

Johnson

2019

Molecular and Cellular Biology

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Eukaryotic ribosome biogenesis requires the action of approximately 200 trans-acting factors and the incorporation of 79 ribosomal proteins (RPs). The delivery of RPs to preribosomes is a major challenge for the cell because RPs are often highly basic and contain intrinsically disordered regions prone to nonspecific interactions and aggregation. To counteract this, eukaryotes developed dedicated chaperones for certain RPs that promote their solubility and expression, often by binding eukaryote-specific extensions of the RPs. Rps2 (uS5) is a universally conserved RP that assembles into nuclear pre-40S subunits. However, a chaperone for Rps2 had not been identified. Our laboratory previously characterized Tsr4 as a 40S biogenesis factor of unknown function. Here, we report that Tsr4 cotranslationally associates with Rps2. Rps2 harbors a eukaryote-specific N-terminal extension that is critical for its interaction with Tsr4. Moreover, Tsr4 perturbation resulted in decreased Rps2 levels and phenocopied Rps2 depletion. Despite Rps2 joining nuclear pre-40S particles, Tsr4 appears to be restricted to the cytoplasm. Thus, we conclude that Tsr4 is a cytoplasmic chaperone dedicated to Rps2.

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“…Based on data from sequence analyses, PDCD2 is thought to have arose from a duplication of the PDCD2L gene prior to the divergence of animals, fungi, and plants from a common ancestor (28). Interestingly, it was recently found that the Drosophila homolog of PDCD2, Zfrp8, interacts with Rps2 (52). Considering the seemingly similar functions ascribed to human PDCD2L and Drosophila PDCD2 (Zfrp8), we examined whether human PDCD2 contributes to ribosome biogenesis and potentially acts redundantly to PDCD2L.…”

Section: Fig 3 Pdcd2l Associates With Late 40s Precursors (A) Gfp-pdmentioning

confidence: 99%

Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

Landry-Voyer

Bilodeau

Bergeron

et al. 2016

Molecular and Cellular Biology

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c Protein arginine methyltransferase 3 (PRMT3) forms a stable complex with 40S ribosomal protein S2 (RPS2) and contributes to ribosome biogenesis. However, the molecular mechanism by which PRMT3 influences ribosome biogenesis and/or function still remains unclear. Using quantitative proteomics, we identified human programmed cell death 2-like (PDCD2L) as a novel PRMT3-associated protein. Our data suggest that RPS2 promotes the formation of a conserved extraribosomal complex with PRMT3 and PDCD2L. We also show that PDCD2L associates with 40S subunit precursors that contain a 3=-extended form of the 18S rRNA (18S-E pre-rRNA) and several pre-40S maturation factors. PDCD2L shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner using a leucine-rich nuclear export signal that is sufficient to direct the export of a reporter protein. Although PDCD2L is not required for the biogenesis and export of 40S ribosomal subunits, we found that PDCD2L-null cells accumulate free 60S ribosomal subunits, which is indicative of a deficiency in 40S subunit availability. Our data also indicate that PDCD2L and its paralog, PDCD2, function redundantly in 40S ribosomal subunit production. Our findings uncover the existence of an extraribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits.

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Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation

Cited by 12 publications

References 68 publications

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

Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rps2 in Saccharomyces cerevisiae

Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

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