MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development
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View abstract on PubMed
Summary
This summary is machine-generated.The MYC oncogene activates pseudouridine synthase 7 (PUS7) in cancer, which helps cells survive stress by boosting amino acid production and stress responses via ATF4. Targeting PUS7 may treat MYC-driven cancers.
Area Of Science
- Molecular Biology
- Cancer Biology
- RNA Modifications
Background
- Pseudouridylation, catalyzed by pseudouridine synthases (PUS), is a common RNA modification impacting RNA stability and function.
- Altered RNA metabolism is a hallmark of cancer, suggesting a role for pseudouridylation in tumor development.
Purpose Of The Study
- To investigate the role of pseudouridylation in MYC-driven cancers.
- To elucidate the functional link between MYC, PUS7, and cancer cell survival.
Main Methods
- Analysis of PUS7 expression in MYC-driven cancers.
- Investigating the impact of PUS7 on cancer cell growth and stress responses.
- Identifying downstream mediators of PUS7 activity, including ATF4.
- Studying the effect of PUS7 on mRNA pseudouridylation and translation.
Main Results
- MYC oncoproteins upregulate PUS7 expression during cancer development.
- PUS7 is essential for the growth and survival of MYC-driven cancer cells by promoting stress responses and amino acid metabolism.
- ATF4 is a key downstream mediator, and its induction by MYC or stress requires PUS7.
- PUS7-mediated pseudouridylation of MCTS1 mRNA enhances its translation, driving ATF4 expression.
Conclusions
- MYC activates an mRNA pseudouridylation program via PUS7 to mitigate cellular stress during cancer progression.
- This program facilitates metabolic reprogramming and adaptive responses, crucial for cancer cell survival.
- Targeting PUS7 presents a potential therapeutic strategy for MYC-driven cancers.
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