RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging synaptosomes

Chen, Bei Jun; Ueberham, Uwe; Kirazov, L.; Kirazov, E.; Knobloch, Mara; Bochmann, Jana; Jendrek, Renate; Takenaka, Konii; Bliim, Nicola; Arendt, Thomas; Janitz, Michael

doi:10.1016/j.neurobiolaging.2017.04.005

Cited by 20 publications

(25 citation statements)

References 52 publications

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“…Indeed, the synaptic transcriptome can be modulated by circadian cycles, alcohol exposure, aging and in schizophrenia. 64,[66][67][68] Interestingly, comparison of synaptoneurosomes to homogenized forebrain revealed that 70% of all synapse localized transcripts were altered at least 2-fold with daily circadian cycles. Ninety-three percent of oscillating transcripts showed this behavior only in synaptoneurosomes.…”

Section: Local Translation In Axonsmentioning

confidence: 99%

“…However, the synaptic transcriptome is not static. Indeed, the synaptic transcriptome can be modulated by circadian cycles, alcohol exposure, aging and in schizophrenia 64,66‐68 . Interestingly, comparison of synaptoneurosomes to homogenized forebrain revealed that 70% of all synapse localized transcripts were altered at least 2‐fold with daily circadian cycles.…”

Section: Rna Localization and Local Translation In Neuronsmentioning

confidence: 99%

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Local gene regulation in radial glia: Lessons from across the nervous system

D’Arcy

Silver

2020

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Radial glial cells (RGCs) are progenitors of the cerebral cortex which produce both neurons and glia during development. Given their central role in development, RGC dysfunction can result in diverse neurodevelopmental disorders. RGCs have an elongated bipolar morphology that spans the entire radial width of the cortex and ends in basal endfeet connected to the pia. The basal process and endfeet are important for proper guidance of migrating neurons and are implicated in signaling. However, endfeet must function at a great distance from the cell body. This spatial separation suggests a role for local gene regulation in endfeet. Endfeet contain a local transcriptome enriched for cytoskeletal and signaling factors. These localized mRNAs are actively transported from the cell body and can be locally translated in endfeet. Yet, studies of local gene regulation in RGC endfeet are still in their infancy. Here, we draw comparisons of RGCs with foundational work in anatomically and phylogenetically related cell types, neurons and astrocytes. Our review highlights a striking overlap in the types of RNAs localized, as well as principles of local translation between these three cell types. Thus, studies in neurons, astrocytes and RGCs can mutually inform an understanding of RNA localization across the nervous system.

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Section: Local Translation In Axonsmentioning

confidence: 99%

Section: Rna Localization and Local Translation In Neuronsmentioning

confidence: 99%

Local gene regulation in radial glia: Lessons from across the nervous system

D’Arcy

Silver

2020

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“…The transcriptomes of mammalian brains show widespread changes during aging [ 6 ]. In addition to changes in transcript expression and the usage of alternative isoforms and promoters of protein-coding genes [ 114 , 115 , 116 , 117 ], quantitative and qualitative changes in the non-coding transcriptome also occur with age [ 115 , 118 ]. Epigenetic alterations inherent to the aging process, such as altered patterns of histone post-translational modifications and DNA methylation, have been considered as the basis for an aged transcriptome [ 4 , 8 ].…”

Section: Lncrna-mediated Processes In the Pathogenesis Of Neurodegmentioning

confidence: 99%

Long Non-Coding RNAs in Neuronal Aging

Fernandes

Bitar

Jacobs

et al. 2018

ncRNA

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The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.

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“…We recently determined local transcriptome changes in synaptosome fractions from young and aging mice using RNA sequencing technique [ 3 ]. This study provides, for the first time, insights into age-related changes in gene expression profiles that encode proteins and non-coding transcripts with unprecedented resolution.…”

mentioning

confidence: 99%

“…Our comparative analysis revealed that the majority of the differentially expressed genes, involved in the aging process within the synapses, are novel and their RNA products do not have protein coding capacity. In addition, a significant proportion of these unannotated genes was identified as putative lncRNAs, an RNA species previously identified as important regulatory molecules in the maintenance of neuronal functionality [ 3 ].…”

mentioning

confidence: 99%