The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules
Open accessAbstract
The inflammatory response plays out over time in a reproducible and organized way after an initiating stimulus. Here we show that genes activated in cultured mouse fibroblasts in response to the cytokine tumor necrosis factor could be categorized into roughly three groups, each with different induction kinetics. Although differences in transcription were important in determining the grouping of these genes, differences in mRNA stability also exerted a strong influence on the temporal order of gene expression, in some cases overriding that of transcriptional control elements. Transcripts of mRNA expressed early had abundant AU-rich elements in their 3' untranslated regions, whereas those expressed later had fewer. Thus, mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of gene expression induced by proinflammatory cytokines.
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Genes may have evolved specific combinations of mRNA and protein half-lives under functional constraints.
“Genes may have evolved specific combinations of mRNA and protein half-lives under functional constraints 20,29-31 .”
From Global quantification of mammalian gene expression control (2011) · cites this paper as [31]
The Results section ('Relative mRNA stability is encoded in the genome'; page unavailable) links differences in mRNA stability to sequence elements in the genes. It does not address protein half-lives or show that particular combinations of mRNA and protein half-lives evolved under functional constraints. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMany fast responding genes have short protein and/or mRNA half-lives.
“These observations are consistent with the idea that many fast responding genes have short protein and/or mRNA half-lives 20,30,31,39 .”
From Global quantification of mammalian gene expression control (2011) · cites this paper as [31]
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- Authors
- Hao, S., & Baltimore, D.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Baltimore, David
- ORCID
- Baltimore, David
- Venue
- Nature Immunology
- Published
- 2009-02-08
- Volume
- 10
- Issue
- 3
- Pages
- 281-288
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2775040
- OpenAlex
- W2099029060
- Cited by
- 480
- References
- 48
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 16 · 2023: 17 · 2022: 21 · 2021: 30 · 2020: 31 · 2019: 22 · 2018: 19 · 2017: 28 · 2016: 31 · 2015: 36 · 2014: 34 · 2013: 45 · 2012: 41
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM039458)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- mRNA stability, gene expression kinetics, inflammation, TNF-α, inflammatory cytokines, AU-rich elements, 3' untranslated region, transcriptional regulation, mouse fibroblasts, inflammatory gene expression
- MeSH terms
- Animals, Dactinomycin, Gene Expression Regulation, Humans, Inflammation, Macrophages, Mice, Inbred C57BL, RNA, Messenger, Tumor Necrosis Factor-alpha, Cluster Analysis, 3T3 Cells, Inflammation Mediators, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA Stability, Mice
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