Evidence map›Paper›PMID 39258545›Full record

ArticleNucleic acids research2024

CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver.

Hong-Yu Li, Min Wang, Xiaoyu Jiang, Yaobin Jing, Zeming Wu, Yifang He, Kaowen Yan, Shuhui Sun, Shuai Ma, Zhejun Ji and 6 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
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  12. Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025
    Review
  13. Review
  14. Review
  15. Article
  16. Causality of Aging Hallmarks.Aging and disease · 2025
    Review
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

16 authors.

Hong-Yu LiKey Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Min WangState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Xiaoyu JiangState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.ORCID 0009-0000-1474-9010
Yaobin JingInternational center for Aging and Cancer, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China.ORCID 0009-0003-9304-0799
Zeming WuState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Yifang HeState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Kaowen YanState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Shuhui SunState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.ORCID 0000-0003-1051-4067
Shuai MaState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Zhejun JiState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Si WangAdvanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China.
Juan Carlos Izpisua BelmonteAltos Labs, Inc., San Diego, CA 94022, USA.
Jing QuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.ORCID 0000-0002-3988-5067
Weiqi ZhangCAS key laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.ORCID 0000-0002-8885-5104
Taotao WeiKey Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Guang-Hui LiuState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.ORCID 0000-0001-9289-8177

Funding

Capital Medical University 12300927CAS Project for Young Scientists in Basic Research YSBR-076CAS Special Research Assistant (SRA) Program, Young Elite Scientists Sponsorship Program by CAST 2023QNRC001CAS Youth Interdisciplinary Team, Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes JYY2023-13Chinese Academy of Sciences CAS-WX2022SDC-XK14Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team BPHR202203105Initiative Scientific Research Program, Institute of Zoology, Chinese Academy of Sciences 2023IOZ0102Key Research and Development Project of Hainan Province 2023ICAC-YANFANational Key Research and Development Program of China 2020YFA0112200National Key Research and Development Program of China 2020YFA0804000National Natural Science Foundation of China 81921006New Cornerstone Science Foundation through the XPLORER PRIZE 2021-1045Project for Technology Development of Beijing-affiliated Medical Research Institutes 11000023T000002036310Science and Technology Platform Construction Project of Hainan Province 2023ICAC-YUNXINGYouth Innovation Promotion Association 2023092
6 · The paper itself

Abstract

Dysfunction of the ribosome manifests during cellular senescence and contributes to tissue aging, functional decline, and development of aging-related disorders in ways that have remained enigmatic. Here, we conducted a comprehensive CRISPR-based loss-of-function (LOF) screen of ribosome-associated genes (RAGs) in human mesenchymal progenitor cells (hMPCs). Through this approach, we identified ribosomal protein L22 (RPL22) as the foremost RAG whose deficiency mitigates the effects of cellular senescence. Consequently, absence of RPL22 delays hMPCs from becoming senescent, while an excess of RPL22 accelerates the senescence process. Mechanistically, we found in senescent hMPCs, RPL22 accumulates within the nucleolus. This accumulation triggers a cascade of events, including heterochromatin decompaction with concomitant degradation of key heterochromatin proteins, specifically heterochromatin protein 1γ (HP1γ) and heterochromatin protein KRAB-associated protein 1 (KAP1). Subsequently, RPL22-dependent breakdown of heterochromatin stimulates the transcription of ribosomal RNAs (rRNAs), triggering cellular senescence. In summary, our findings unveil a novel role for nucleolar RPL22 as a destabilizer of heterochromatin and a driver of cellular senescence, shedding new light on the intricate mechanisms underlying the aging process.

Indexed as

Cell NucleolusCellular SenescenceChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCRISPR-Cas SystemsHeterochromatinRibosomal ProteinsHumansMesenchymal Stem CellsRepressor ProteinsRNA-Binding ProteinsRNA, RibosomalCBX3 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneHeterochromatinRepressor ProteinsRibosomal ProteinsRNA-Binding ProteinsRNA, RibosomalRPL22 protein, human

Identifiers

PMID39258545
PMCPMC11514463

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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.