Transcript and protein expression decoupling reveals RNA binding proteins and miRNAs as potential modulators of human aging
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Background: In studies of development and aging, the expression of many genes has been shown to undergo drastic changes at mRNA and protein levels. The connection between mRNA and protein expression level changes, as well as the role of posttranscriptional regulation in controlling expression level changes in postnatal development and aging, remains largely unexplored. Results: Here, we survey mRNA and protein expression changes in the prefrontal cortex of humans and rhesus macaques over developmental and aging intervals of both species’ lifespans. We find substantial decoupling of mRNA and protein expression levels in aging, but not in development. Genes showing increased mRNA/protein disparity in primate brain aging form expression patterns conserved between humans and macaques and are enriched in specific functions involving mammalian target of rapamycin ( mTOR ) signaling, mitochondrial function and neurodegeneration. Mechanistically, aging-dependent mRNA/protein expression decoupling could be linked to a specific set of RNA binding proteins and, to a lesser extent, to specific microRNAs. Conclusions: Increased decoupling of mRNA and protein expression profiles observed in human and macaque brain aging results in specific co-expression profiles composed of genes with shared functions and shared regulatory signals linked to specific posttranscriptional regulators. Genes targeted and predicted to be targeted by the aging-dependent posttranscriptional regulation are associated with biological processes known to play important roles in aging and lifespan extension. These results indicate the potential importance of posttranscriptional regulation in modulating aging-dependent changes in humans and other species.
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Discordance or decoupling in mRNA and protein expression of the same genes has been reported in human aging and neurodegenerative disorders such as tauopathy and AD.
“The discordance or decoupling in mRNA and protein expression of the same genes has been reported in studies with human aging [67] and neurodegenerative disorders such as tauopathy [68] and AD [69]”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [67]
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- Authors
- Wei, Y.-N., Hu, H.-Y., Xie, G.-C., Fu, N., Ning, Z.-B., Zeng, R., & Khaitovich, P.
- Affiliations
- Chinese Academy of Sciences (CN)
- Skolkovo Institute of Science and Technology (RU)
- Corresponding author
- Zeng, Rong
- Khaitovich, Philipp
- Venue
- Genome Biology
- Published
- 2015-02-22
- Volume
- 16
- Issue
- 1
- Pages
- 41-41
- ISSN
- 1465-6906 (ISSN-L)
- PMC
- PMC4375924
- OpenAlex
- W1989635088
- Cited by
- 117
- References
- 106
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 27 · 2023: 11 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 8
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- uO Research (University of Ottawa) (submittedVersion, public-domain)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Natural Science Foundation of China (31171232, 91331203)
- Chinese Academy of Sciences (XDB13010200)
- Ministry of Science and Technology of the People's Republic of China (2011CB910200)
- Bureau of International Cooperation, Chinese Academy of Sciences (GJHZ201313)
- Russian Science Foundation (14‐28‐00234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- post-transcriptional regulation, human aging, rhesus monkeys, prefrontal cortex, RNA-binding proteins, microRNA, mTOR signaling, mitochondrial function, neurodegeneration, gene co-expression, lifespan extension, developmental gene expression
- MeSH terms
- Aging, Animals, Humans, Macaca mulatta, RNA, Messenger, Signal Transduction, RNA-Binding Proteins, Prefrontal Cortex, Gene Expression Regulation, Developmental, Gene Expression Profiling, MicroRNAs
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