Conservation of a core neurite transcriptome across neuronal types and species

Kügelgen, Nicolai von; Chekulaeva, Marina

doi:10.1002/wrna.1590

Cited by 33 publications

(44 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GO‐term analysis indicates the overrepresentation of specific cellular components in these compartments: ribosomal subunits, postsynaptic density and mitochondrial respiratory chain complex in the process compartment: extracellular matrix, extracellular space and secretory granule lumen in the somatic compartment (Fig 1D ; Appendix Fig S1 ). Importantly, we observed a very high correlation between our RNA‐seq dataset and a recently published meta‐analysis (von Kugelgen & Chekulaeva, 2020 ) of neurite‐enriched mRNAs derived from 11 independent high coverage datasets (Fig EV2A–E ). Together, these results are consistent with previous large‐scale studies (Poon et al , 2006 ; Cajigas et al , 2012 ; Zappulo et al , 2017 ; Kuzniewska et al , 2020 ) and suggest that our approach is able to faithfully capture differences in mRNA distribution between neuronal compartments.…”

Section: Resultssupporting

confidence: 67%

“… Pearson's correlation of RNA logFC (Processes vs Somata) under basal conditions to the average of significant log 2 enrichments of genes as of obtained by (von Kugelgen & Chekulaeva, 2020 ) from 11 high coverage datasets describing neuronal localization. The statistical significance of Pearson correlations was calculated in the standard fashion, i.e.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pervasive compartment‐specific regulation of gene expression during homeostatic synaptic scaling

et al. 2021

View full text Add to dashboard Cite

Synaptic scaling is a form of homeostatic plasticity which allows neurons to adjust their action potential firing rate in response to chronic alterations in neural activity. Synaptic scaling requires profound changes in gene expression, but the relative contribution of local and cell-wide mechanisms is controversial. Here we perform a comprehensive multi-omics characterization of the somatic and process compartments of primary rat hippocampal neurons during synaptic scaling. We uncover both highly compartment-specific and correlating changes in the neuronal transcriptome and proteome. Whereas downregulation of crucial regulators of neuronal excitability occurs primarily in the somatic compartment, structural components of excitatory postsynapses are mostly downregulated in processes. Local inhibition of protein synthesis in processes during scaling is confirmed for candidate synaptic proteins. Motif analysis further suggests an important role for trans-acting post-transcriptional regulators, including RNA-binding proteins and microRNAs, in the local regulation of the corresponding mRNAs. Altogether, our study indicates that, during synaptic scaling, compartmentalized gene expression changes might co-exist with neuron-wide mechanisms to allow synaptic computation and homeostasis.

show abstract

Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Pervasive compartment‐specific regulation of gene expression during homeostatic synaptic scaling

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Due to the unique extensive morphology of neurons and their high dependence on intact intracellular protein transport, axonal defects are often thought to precede neurodegeneration [61][62][63][64]. Neurons also possess intricate and expansive transcriptomic profiles with its axons containing hundreds to thousands of mRNAs, including mRNAs of proteins that regulate gene expression in response to local axonal activity [65]. In addition to the main transport machinery such as dynein, kinesin, and their cargos, RBPs also play an indispensable supportive role in maintaining axonal transport.…”

Section: Axonal Transportmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

et al. 2020

View full text Add to dashboard Cite

Heterogenous nuclear ribonucleoproteins (hnRNPs) are a complex and functionally diverse family of RNA binding proteins with multifarious roles. They are involved, directly or indirectly, in alternative splicing, transcriptional and translational regulation, stress granule formation, cell cycle regulation, and axonal transport. It is unsurprising, given their heavy involvement in maintaining functional integrity of the cell, that their dysfunction has neurological implications. However, compared to their more established roles in cancer, the evidence of hnRNP implication in neurological diseases is still in its infancy. This review aims to consolidate the evidences for hnRNP involvement in neurological diseases, with a focus on spinal muscular atrophy (SMA), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), congenital myasthenic syndrome (CMS), and fragile X-associated tremor/ataxia syndrome (FXTAS). Understanding more about hnRNP involvement in neurological diseases can further elucidate the pathomechanisms involved in these diseases and perhaps guide future therapeutic advances.

show abstract

“…It is unclear, however, how much a transcript's somatic level influences its localization in processes, and whether transcripts can be enriched or excluded from the neurites regardless of their somatic abundances. In fact, mRNA localization is often defined based on either the absolute abundance of a transcript in neurites or the relative enrichment in comparison to somata (Kügelgen and Chekulaeva, 2020). These absolute versus relative values can generate significantly different abundance rankings of the mRNAs that comprise local transcriptomes.…”

Section: Introductionmentioning

confidence: 99%

Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

Pérez

Dieck

Álvarez-Castelao

et al. 2021

eLife

View full text Add to dashboard Cite

Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell types is unknown. Here we describe the unbiased transcriptomic characterization of the subcellular compartments of hundreds of single neurons. We separately profiled the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigated mRNA abundances in the soma and dendrites of single glutamatergic and GABAergic neurons. We found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. We observed more cell type-specific features among somatic transcriptomes than their associated dendritic transcriptomes. Finally, using celltype-specific metabolic labeling of isolated neurites, we demonstrated that the processes of glutamatergic and, notably, GABAergic neurons were capable of local translation, suggesting mRNA localization and local translation are general properties of neurons.

show abstract

Conservation of a core neurite transcriptome across neuronal types and species

Abstract: A core transcriptome form neurites was consistently detected across multiple neuronal types and includes mRNAs enriched for components of the translation machinery, mitochondrial proteins, components of the cytoskeleton, and proteins associated with neurite formation.

Cited by 33 publications

References 80 publications

Pervasive compartment‐specific regulation of gene expression during homeostatic synaptic scaling

Pervasive compartment‐specific regulation of gene expression during homeostatic synaptic scaling

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

Contact Info

Product

Resources

About