NF90 coordinately represses the senescence-associated secretory phenotype
Kumiko Tominaga-Yamanaka1, Kotb Abdelmohsen, Jennifer L Martindale
1Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Aging
|November 3, 2012
Summary
RNA-binding protein NF90 acts as a repressor of senescence-associated secretory phenotype (SASP) factors. Reduced NF90 levels in senescent cells allow SASP factor expression, contributing to the aging process.
Area of Science:
- Molecular Biology
- Cell Biology
- Aging Research
Background:
- Cellular senescence is characterized by the senescence-associated secretory phenotype (SASP).
- SASP factors, including cytokines and chemokines, are encoded by mRNAs with regulated stability and translation.
- The precise mechanisms controlling SASP factor expression during senescence are under investigation.
Purpose of the Study:
- To identify RNA-binding proteins that regulate SASP factor expression.
- To investigate the role of RNA-binding protein NF90 in cellular senescence and SASP.
- To elucidate the post-transcriptional mechanisms governing SASP factor production.
Main Methods:
- Utilized two models of human fibroblast senescence (WI-38 and IDH4 cells).
- Investigated the expression and association of RNA-binding protein NF90 with SASP mRNAs.
- Assessed the impact of NF90 levels on SASP factor expression and mRNA translation.
Main Results:
- Identified NF90 as a post-transcriptional repressor of several SASP factors.
- Found high NF90 abundance in proliferating fibroblasts, inhibiting SASP factor expression.
- Observed low NF90 levels in senescent cells, correlating with increased SASP factor expression.
- Demonstrated that NF90 primarily represses SASP mRNA translation, not stability.
Conclusions:
- NF90 plays a crucial role in maintaining low SASP factor levels in non-senescent cells.
- Reduction of NF90 in senescent cells facilitates the rise in SASP factor expression.
- NF90 is a key regulator of the senescence-associated secretory phenotype.
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