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| Status |
Public on Dec 14, 2025 |
| Title |
Function and mechanism of PAPOLA-mediated poly(A) lengthening in leukemia [RIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
The polyadenylation of mRNA is pivotal for mRNA stability and efficient mRNA translation. The length of poly(A) tail is dynamically changed under various physiological conditions; however, the functions and mechanisms of aberrant poly(A) length control in cancers remain poorly understood. Here we uncovered the aberrant lengthening of poly(A) tail and particularly upregulated expression of poly(A) polymerase alpha (PAPOLA) in acute myeloid leukemia (AML), and the elevated PAPOLA expression significantly correlated with unfavorable AML outcomes. We further demonstrated the critical oncogenic functions of PAPOLA-mediated poly(A) lengthening in promoting AML leukemogenesis and leukemia stem cell self-renewal using human primary AML samples, AML cells and various mouse leukemogenesis models. Mechanistically, we identified GSTM2 as a key downstream target of PAPOLA that regulated metabolic reprogramming through the HNE-DLD axis to promote AML initiation and progression. Moreover, PAPOLA inhibitor cordycepin effectively blocked metabolic reprogramming and AML leukemogenesis in vivo. Overall, our study uncovers the novel functional link between aberrant poly(A) lengthening and cellular metabolic reprogramming in AML, and provides a molecular basis for development of an effective therapeutic strategy for AML patients.
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| Overall design |
RNA immunoprecipitation sequencing (RIP-seq) was used to detect RNA interactions with PAPOLA protein in AML cells.
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| Contributor(s) |
Guo S, Lin S |
| Citation missing |
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| Submission date |
Feb 12, 2024 |
| Last update date |
Dec 14, 2025 |
| Contact name |
Siyao Guo |
| E-mail(s) |
guosy6@mail2.sysu.edu.cn
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| Organization name |
The First Affiliated Hospital, Sun Yat-sen University
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| Street address |
No.58 Zhongshan Er Road
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| City |
Guangzhou |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE255668 |
Function and mechanism of PAPOLA-mediated poly(A) lengthening in leukemia |
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| Relations |
| BioProject |
PRJNA1075759 |
