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The Tet2-Upf1 complex modulates mRNA stability under stress conditions
Meiling Xia1,2, Rui Yan2, Wenjuan Wang2
1Departments of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Frontiers in Genetics
|April 24, 2023
Summary
Chronic stress increases cytoplasmic ten-eleven Translocation 2 (Tet2) enzyme, leading to altered RNA 5-hydroxymethylcytosine (5hmC) modifications. This epigenetic change impacts stress-related gene stability and neurodevelopment, offering potential therapeutic targets for depression.
Area of Science:
- Epigenetics
- Neuroscience
- Molecular Biology
Background:
- Environmental stress induces epigenetic changes impacting gene expression and disease pathology.
- Ten-eleven Translocation (Tet) enzymes are crucial epigenetic regulators, modifying DNA and RNA.
- Previous work linked chronic stress to increased cytoplasmic Tet2 in the hippocampus.
Purpose of the Study:
- To investigate the role of cytoplasmic Tet2 in RNA 5-hydroxymethylcytosine (5hmC) modification under chronic mild stress (CMS).
- To identify downstream targets and mechanisms of Tet2 action in stress-related processes.
Main Methods:
- Established a chronic mild stress (CMS) mouse model.
- Detected RNA 5hmC levels using dot blot.
- Verified Tet2 interactions with proteins using co-immunoprecipitation and mass spectrometry.
- Screened target genes and analyzed their expression via cluster analysis, Western blot, and qRT-PCR.
Main Results:
- CMS elevated cytoplasmic Tet2 expression and total RNA 5hmC modification.
- Tet2 was found to interact with the non-sense-mediated mRNA decay (NMD) factor Upf1.
- Tet2 regulated the stability of stress-related genes, including Unc5b mRNA, potentially affecting neurodevelopment.
Conclusions:
- Tet2-mediated RNA 5hmC modification plays a role in regulating mRNA stability in response to chronic stress.
- This pathway represents a potential therapeutic target for stress-related disorders like depression.
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