Evidence map›Paper›PMID 34611297›Full record

ArticleCell death and differentiation2022

RNA-interference screen for p53 regulators unveils a role of WDR75 in ribosome biogenesis.

Pavel Moudry, Katarina Chroma, Sladana Bursac, Sinisa Volarevic, Jiri Bartek

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 4 countries.

Pavel MoudryInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. pavel.moudry@upol.cz.ORCID http://orcid.org/0000-0002-1479-007X
Katarina ChromaInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.ORCID http://orcid.org/0000-0003-0141-0469
Sladana BursacDepartment of Molecular Medicine and Biotechnology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.ORCID http://orcid.org/0000-0002-6478-3409
Sinisa VolarevicDepartment of Molecular Medicine and Biotechnology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.ORCID http://orcid.org/0000-0003-4893-389X
Jiri BartekInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. jb@cancer.dk.ORCID http://orcid.org/0000-0003-2013-7525
Institute of Molecular and Translational Medicine · CZUniversity of Rijeka · HRScience for Life Laboratory · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ribosome biogenesis is an essential, energy demanding process whose deregulation has been implicated in cancer, aging, and neurodegeneration. Ribosome biogenesis is therefore under surveillance of pathways including the p53 tumor suppressor. Here, we first performed a high-content siRNA-based screen of 175 human ribosome biogenesis factors, searching for impact on p53. Knock-down of 4 and 35 of these proteins in U2OS cells reduced and increased p53 abundance, respectively, including p53 accumulation after depletion of BYSL, DDX56, and WDR75, the effects of which were validated in several models. Using complementary approaches including subcellular fractionation, we demonstrate that endogenous human WDR75 is a nucleolar protein and immunofluorescence analysis of ectopic GFP-tagged WDR75 shows relocation to nucleolar caps under chemically induced nucleolar stress, along with several canonical nucleolar proteins. Mechanistically, we show that WDR75 is required for pre-rRNA transcription, through supporting the maintenance of physiological levels of RPA194, a key subunit of the RNA polymerase I. Furthermore, WDR75 depletion activated the RPL5/RPL11-dependent p53 stabilization checkpoint, ultimately leading to impaired proliferation and cellular senescence. These findings reveal a crucial positive role of WDR75 in ribosome biogenesis and provide a resource of human ribosomal factors the malfunction of which affects p53.

Indexed as

Ribosomal ProteinsCell Adhesion MoleculesCell Line, TumorCell NucleolusDEAD-box RNA HelicasesHumansNuclear ProteinsRibosomesRNA PrecursorsTumor Suppressor Protein p53BYSL protein, humanCell Adhesion MoleculesDDX56 protein, humanDEAD-box RNA HelicasesNuclear ProteinsRibosomal ProteinsRNA PrecursorsTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID34611297
PMCPMC8901908
OpenAlexW3202927559

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.