DEAD-box RNA helicase 10 is required for 18S rRNA maturation by controlling the release of U3 snoRNA from pre-rRNA in embryonic stem cells
Ribosome biogenesis plays a pivotal role in maintaining stem cell homeostasis, yet the precise regulatory mechanisms governing this process in mouse embryonic stem cells (mESCs) remain largely unknown. In this investigation, we ascertain that DEAD-box RNA helicase 10 (DDX10) is indispensable for upholding cellular homeostasis and the viability of mESCs. Positioned predominantly at the nucleolar dense fibrillar component (DFC) and granular component (GC), DDX10 predominantly binds to 45S ribosomal RNA (rRNA) and orchestrates ribosome biogenesis. Degradation of DDX10 prevents the release of U3 snoRNA from pre-rRNA, leading to perturbed pre-rRNA processing and compromised maturation of the 18S rRNA, thereby disrupting the biogenesis of the small ribosomal subunit. Moreover, DDX10 participates in the process of liquid-liquid phase separation (LLPS), which is necessary for efficient ribosome biogenesis. Notably, the NUP98-DDX10 fusion associated with acute myelocytic leukemia (AML) alters the cellular localization of DDX10 and results in loss of ability to regulate pre-rRNA processing. Collectively, this study reveals the critical role of DDX10 as a pivotal regulator of ribosome biogenesis in mESCs.
Authors
- Xiangting Wang (ORCID: https://orcid.org/0000-0003-2106-3425)
- Jiapeng Liao (ORCID: https://orcid.org/0000-0001-7640-5977)
- Yawei Song (ORCID: https://orcid.org/0000-0003-3456-6881)
- Yanjiang Liu (ORCID: https://orcid.org/0009-0000-0115-7083)
- Yue-Qin Chen
- Qingqing Cai (ORCID: https://orcid.org/0000-0001-5447-3282)
- Hongjie Yao (ORCID: https://orcid.org/0000-0003-2144-0147)
- Yu Fu (ORCID: https://orcid.org/0000-0003-0934-8655)
- Xiaofei Zhang (ORCID: https://orcid.org/0000-0002-2564-9258)
- Heying Li (ORCID: https://orcid.org/0009-0006-5025-8941)
- Wentao Wang (ORCID: https://orcid.org/0000-0003-3913-4455)
- Xiaorong Zhang (ORCID: https://orcid.org/0000-0002-8550-1052)
- Lisha Wang (ORCID: https://orcid.org/0000-0002-6482-1073)
- Shengxiong Yang (ORCID: https://orcid.org/0000-0002-6614-0044)
- Xiuqin Wang
- Qian Zhao (ORCID: https://orcid.org/0000-0002-1220-3468)
- Gongcheng Hu (ORCID: https://orcid.org/0000-0002-6498-0509)
- Yuli Lu (ORCID: https://orcid.org/0000-0001-8156-8682)
- Qiuling Huang
- Wenjing Guo
Institutions
- University of Science and Technology of China (CN)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Guangzhou Chemistry (China) (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41467-024-53822-0
- Citations
- 5
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- National Natural Science Foundation of China