CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver DOI Creative Commons
Hongyu Li, Min Wang, Xiaoyu Jiang

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(19), P. 11481 - 11499

Published: Sept. 11, 2024

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

Language: Английский

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging DOI
Shuai Ma,

Zhejun Ji,

Bin Zhang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(24), P. 7025 - 7044.e34

Published: Nov. 1, 2024

Language: Английский

Citations

13
Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases DOI
Zeming Wu, Jing Qu, Guang‐Hui Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 979 - 1000

Published: Oct. 3, 2024

Language: Английский

Citations

9
RIG-I-driven CDKN1A stabilization reinforces cellular senescence DOI
Cui Wang, Xiaofei Jiang, Hongyu Li

et al.

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

Citations

0
CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver DOI Creative Commons
Hongyu Li, Min Wang, Xiaoyu Jiang

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(19), P. 11481 - 11499

Published: Sept. 11, 2024

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

Language: Английский

Citations

2