The beta‐isoform of the BRCA2 and CDKN1A(p21)‐interacting protein (BCCIP) stabilizes nuclear RPL23/uL14

Wyler, Emanuel; Wandrey, Franziska; Badertscher, Lukas; Montellese, Christian; Alper, Daniel; Kutay, Ulrike

doi:10.1016/j.febslet.2014.08.013

Cited by 28 publications

(29 citation statements)

References 26 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, Bcp1 is reported to have negative genetic interaction with both efl1 and sdo1 mutants (30). BCCIP␤, the human homolog of Bcp1, was shown to interact with eIF6 and Rpl23 as a small complex, but depletion of BCCIP␤ did not show deficiency in 60S biogenesis (31). These data point to a functional significance of Bcp1 with Rpl23 in the ribosome biogenesis pathway.…”

mentioning

confidence: 88%

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Ting

Johnson

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Linda SpremulliEukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.The ribosome is a large macromolecular complex responsible for decoding cellular genetic information into proteins. There are two ribosomal subunits; in the eukaryotes, they are the (60S) large subunit and the small (40S) subunit, each composed of both rRNAs and ribosomal proteins. In eukaryotic cells, the assembly of ribosomes occurs in the nucleolus, a subcompartment of the nucleus devoted to ribosome biogenesis. rRNAs are transcribed by RNA polymerase I and III, and the initial assembly and processing events occur co-transcriptionally. The mRNAs of ribosomal proteins are transcribed in the nucleus by RNA polymerase II and translated in the cytoplasm. Consequently, the ribosomal proteins must be imported into the nucleus for assembly with the rRNAs. After ribosome assemblies have achieved a certain stage of maturation, export factors are loaded to direct these huge complexes to cross the nuclear membrane through the nuclear pore complexes (1-6). In the cytoplasm, ribosomes undergo additional steps in the maturation process; the trans-acting factors that are exported with nascent ribosomal subunits need to be stripped off, additional ribosomal proteins are added, and in the case of the 40S subunit, the final rRNA processing occurs (7,8). The synthesis of ribosomes requires the coordination of many non-ribosomal trans-acting factors at different stages for this pathway to be completed. About 200 trans-acting factors are involved in rRNA processing, rRNA folding, protein loading, and export. To date, more trans-acting factors have continued to be identified (7, 9, 10).BCP1 is an essential gene involved in the export of Mss4 (11), a phosphatidylinositol (PI) 2 4-phosphate 5-kinase that catalyzes the phosphorylation of PI4-phosphate and acts with the PI4-kinase, Stt4p, at the plasma membrane to generate PI4,5P 2 (12, 13). Phosphoinositols are critical small signal...

show abstract

mentioning

confidence: 88%

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Ting

Johnson

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The function of the human Bcp1 homologue (BCCIP) is unclear and may not be equivalent to that of the yeast protein. The BCCIPβ isoform seems to have a role in ribosome biogenesis via its interaction with Rpl23, but its depletion does not impair the 60S synthesis pathway [13]. Rpl23 is also the major binding site of Tif6, an anti-association factor that prevents premature association of the not-fully mature 60S subunits with the 40S subunits [14].…”

Section: Introductionmentioning

confidence: 99%

Conformational Flexibility of Proteins Involved in Ribosome Biogenesis: Investigations via Small Angle X-ray Scattering (SAXS)

et al. 2018

View full text Add to dashboard Cite

Abstract:The dynamism of proteins is central to their function, and several proteins have been described as flexible, as consisting of multiple domains joined by flexible linkers, and even as intrinsically disordered. Several techniques exist to study protein structures, but small angle X-ray scattering (SAXS) has proven to be particularly powerful for the quantitative analysis of such flexible systems. In the present report, we have used SAXS in combination with X-ray crystallography to highlight their usefulness at characterizing flexible proteins, using as examples two proteins involved in different steps of ribosome biogenesis. The yeast BRCA2 and CDKN1A-interactig protein, Bcp1, is a chaperone for Rpl23 of unknown structure. We showed that it consists of a rigid, slightly elongated protein, with a secondary structure comprising a mixture of alpha helices and beta sheets. As an example of a flexible molecule, we studied the SBDS (Shwachman-Bodian-Diamond Syndrome) protein that is involved in the cytoplasmic maturation of the 60S subunit and constitutes the mutated target in the Shwachman-Diamond Syndrome. In solution, this protein coexists in an ensemble of three main conformations, with the N-and C-terminal ends adopting different orientations with respect to the central domain. The structure observed in the protein crystal corresponds to an average of those predicted by the SAXS flexibility analysis.

show abstract

“…Similarly, the Ankyrin-repeat protein Yar1 is cotranslationally recruited to nascent r-protein S3 (uS3) and protects uS3 from aggregation as well as escorts uS3 into the nucleus (10,14,15). The necessity of dedicated chaperones to escort nascent r-proteins appears to be evolutionarily conserved, as demonstrated by binding of Bcp1 and its human homolog, BCCIP␤, to r-protein L23 (uL14) in S. cerevisiae and human cells, respectively (16,17). As yet, however, only a few dedicated r-protein chaperones have been identified, mostly in the budding yeast S. cerevisiae (18).…”

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

View full text Add to dashboard Cite

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.

show abstract

The beta‐isoform of the BRCA2 and CDKN1A(p21)‐interacting protein (BCCIP) stabilizes nuclear RPL23/uL14

Cited by 28 publications

References 26 publications

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Conformational Flexibility of Proteins Involved in Ribosome Biogenesis: Investigations via Small Angle X-ray Scattering (SAXS)

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

Contact Info

Product

Resources

About