Related Experiment Video

Updated: Aug 9, 2025

Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry
08:45

Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry

Published on: April 21, 2022

2.4K

Conserved reduction of m6A RNA modifications during aging and neurodegeneration is linked to changes in synaptic

Ricardo Castro-Hernández1, Tea Berulava1, Maria Metelova1

  • 1Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, 37077 Göttingen, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|February 22, 2023
PubMed

Insights

N6-methyladenosine (m6A) RNA methylation decreases in aged mice and Alzheimer's disease patients, impacting synaptic function and protein synthesis. This suggests m6A's role in cognitive decline.

Area of Science:

  • Neuroscience
  • Epigenetics
  • Molecular Biology

Background:

  • N6-methyladenosine (m6A) is a crucial mRNA modification involved in brain development and cognition.
  • The specific role of m6A in synaptic plasticity during cognitive decline remains largely unexplored.

Purpose of the Study:

  • To investigate the role of m6A RNA methylation in synaptic plasticity and cognitive decline.
  • To compare m6A levels in young versus aged mice and in human Alzheimer's disease patients versus controls.

Main Methods:

  • Methylated RNA immunoprecipitation sequencing (m6A-IP-seq) to profile the m6A epitranscriptome in mouse hippocampal subregions and anterior cingulate cortex.
  • Comparative analysis of m6A RNA methylation in human cingulate cortex tissue from healthy individuals and Alzheimer's disease patients.
  • Proximity ligation assays to assess synaptic protein synthesis.

Main Results:

  • Aged mice exhibited decreased m6A levels compared to young mice.
  • Alzheimer's disease patients showed reduced m6A RNA methylation in cingulate cortex tissue compared to cognitively intact subjects.
  • Common m6A changes in aged mice and AD patients were observed in transcripts vital for synaptic function, including CAMKII and GLUA1.
  • Reduced m6A levels correlated with decreased synaptic protein synthesis and impaired synaptic function.

Conclusions:

  • m6A RNA methylation regulates synaptic protein synthesis, potentially through key synaptic genes like CAMKII and GLUA1.
  • Decreased m6A levels are associated with cognitive decline in aging and Alzheimer's disease.
  • m6A represents a potential therapeutic target for age-related cognitive impairment and Alzheimer's disease.
Keywords:
Alzheimer’s diseaseRNA-methylationepi-transcriptomicsepigeneticsneuro-epigenetics

More Related Videos

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models08:33

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models

Published on: March 24, 2019

7.6K
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology14:57

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

Published on: March 23, 2011

94.3K

Related Concept Videos

RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.8K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.7K
Aging01:26

Aging

Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
133
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.7K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.1K