Evidence map›Paper›PMID 39146182›Full record

ArticleCell reports2024

RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4.

Hannah N W Weinstein, Kevin Hu, Lisa Fish, Yih-An Chen, Paul Allegakoen, Julia H Pham, Keliana S F Hui, Chih-Hao Chang, Meltem Tutar, Lorena Benitez-Rivera and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Ribosome-directed cancer therapies: the tip of the iceberg?Trends in pharmacological sciences · 2025
    Review
  14. Ribosomal protein paralogues in ribosome specialization.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  15. High-resolution reconstruction of aRNA (New York, N.Y.) · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Hannah N W WeinsteinDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Kevin HuDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Lisa FishDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Yih-An ChenDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Paul AllegakoenDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Julia H PhamDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Keliana S F HuiDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Chih-Hao ChangDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Meltem TutarDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Lorena Benitez-RiveraDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Maria B BacoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hanbing SongDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Andrew O GiacomelliTumor Immunotherapy Program, Princess Margaret Cancer Center, Toronto, ON, Canada.
Francisca VazquezBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Mahmoud GhandiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hani GoodarziDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Franklin W HuangDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. Electronic address: franklin.huang@ucsf.edu.

Funding

Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Immunity and Stress (RESPOND)U19CA214253 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAIMAN, CHRISTOPHER ALAN · 2018 to 2023
$16.8M
Precision Interception of Aggressive Prostate Cancer in African American MenP20CA233255 · NCI · DANA-FARBER CANCER INST · PI REBBECK, TIMOTHY R · 2018 to 2020
$3.2M
Investigating the mechanisms of driver genes associated with ancestry and aggressiveness in prostate cancerR01CA248920 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Joshua D Campbell · 2021 to 2026
$2.9M
The RNA structural code underlying pathological regulation of RNA splicing in metastasisR01CA244634 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOODARZI, HANI · 2021 to 2025
$1.8M
CSRD VA I01 CX002444NCI NIH HHS P20 CA233255NCI NIH HHS R01 CA244634NCI NIH HHS R01 CA248920NCI NIH HHS U19 CA214253
6 · The paper itself

Abstract

Microsatellite instability-high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intact TP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation in RPL22, a ribosomal protein. Here, we identified RPL22 as a modulator of MDM4 splicing through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses the expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction.

Indexed as

Cell Cycle ProteinsRibosomal ProteinsAlternative SplicingAnimalsCell Line, TumorCell ProliferationExonsGene Expression Regulation, NeoplasticHumansImidazolesMiceNeoplasmsNuclear ProteinsPiperazinesProto-Oncogene ProteinsTumor Suppressor Protein p53Cell Cycle ProteinsImidazolesMDM4 protein, humanNuclear ProteinsPiperazinesProto-Oncogene ProteinsRibosomal ProteinsTumor Suppressor Protein p53alternative splicingCP: CancerCP: Molecular biologyMDM4MDM4 exon 6 inclusionmicrosattelite instability-highMSI-Hp53ribosomal proteinsRPL22RPL22 p.K15fstumor suppressor

Identifiers

PMID39146182
PMCPMC12035866

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Registered trials

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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.