Local translation in neuronal processes

Biever, Anne; Donlin-Asp, Paul G.; Schuman, Erin M.

doi:10.1016/j.conb.2019.02.008

Cited by 107 publications

(96 citation statements)

References 77 publications

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“…As predicted, we identified significant enrichment of genes preferentially expressed in synaptic terminals within 'neuropil spots' that contained no cell bodies. Given that robust evidence now supports the existence of localized mRNA expression and protein synthesis in both the pre-and post-synaptic compartments (Biever et al, 2019) , directly studying neuropil-enriched transcripts in human brain has the potential to provide novel insights about expression of locally translated synaptic genes that may be missed with snRNA-seq analysis of dissociated nuclear preparations. Better understanding the regulation of synaptically localized transcripts in human cortex is important because the regulation of synaptic proteins controls neuronal homeostasis and drives synaptic plasticity (Biever et al, 2019) .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Maynard

Collado‐Torres

Weber³

et al. 2020

Preprint

141

326

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We used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially-defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research ( http://research.libd.org/spatialLIBD ).

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Section: Discussionmentioning

confidence: 99%

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Maynard

Collado‐Torres

Weber³

et al. 2020

Preprint

141

326

View full text Add to dashboard Cite

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“…Finally the local translation of these long synaptic proteins encoding cell adhesion molecules, scaffolding proteins, channels and receptors may be responsible for changes in synaptic strength following synaptic activity as the synapses grow on both the pre-and post-synaptic sides during development and due to experience. Once localized to the synapse these mRNAs are likely maintained in a translationally repressed state during the stage of elongation until suitable synaptic signals release this repression [241][242][243][244][245][246][247][248] . This has been suggested to be a common mechanism regulating protein synthesis in neuronal processes 35,[249][250][251] .…”

Section: A Seventh Common Upstream Regulatory Pathway Dmd (Dystrophimentioning

confidence: 99%

FMRP binding to a ranked subset of long genes is revealed by coupled CLIP and TRAP in specific neuronal cell types

Driesche

Sawicka

Zhang

et al. 2019

Preprint

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Highlights 1. We have created a mouse model in which endogenous FMRP can be conditionally tagged.2. Using tag-specific CLIP we describe ranked and specific sets of in vivo FMRP mRNA targets in two types of neurons.3. This ranking was used to reveal that FMRP regulates mRNAs with long coding sequences.4. FMRP mRNA targets in Purkinje cells, including the top-ranked IP3 receptor, are related to cell-autonomous Fragile X phenotypes. 5.We have updated our previous list of whole mouse brain FMRP mRNA targets with more replicates, deeper sequencing and improved analysis 6. The use of tagged FMRP in less abundant cell populations allowed identification of novel mRNA targets missed in a whole brain analysis

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“…Since the subcellular components, i.e. dendrites and axons, contain mRNA and the translational machineries separately from those in soma (Biever et al, 2019), a true picture of brain regional transcriptome can be inevitably complex. In future studies, it will be useful to take heterogeneity into account and to use a more individualized approach for analyzing the transcriptome, e.g.…”

Section: Implications For Future Work On Genotype-dependent Differencmentioning

confidence: 99%

Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene

Kawano

et al. 2019

Preprint

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In patients with the brain disorder dystonia, body movement is severely affectedwith involuntary muscle contractions and abnormal postures, causing extensive deterioration of the patient's quality of life. The most common inherited form of this disorder is DYT1 dystonia, which is caused by a mutation in TOR1A gene and autosomal dominant. The molecular mechanisms that underlie the effects of the TOR1A mutation on brain function remain unclear. To understand these, we examined the gene expression profiles (transcriptome) in four brain regions (cerebral cortex, hippocampus, striatum and cerebellum) in a mouse model, the heterozygous ΔE-torsinA knock-in mice which genetically reproduce the mutation in DYT1 dystonia. The samples were obtained at 2 to 3 weeks of age, a period during which synaptic abnormalities have been reported. Pairwise comparisons of brain regions revealed differential gene expression irrespective of genotype. A comparison of heterozygous to wild-type mice failed to reveal genotype-dependent differences in gene expression in any of the four brain regions when examined individually. However, genotype-dependent differences became apparent when the information for all brain regions was combined. These results suggest that any changes in the transcriptome within a brain region were subtle at this developmental stage, but that statistically significant changes occur across all brain regions. Such changes in the transcriptome, although subtle in degree, could underlie the processes that give rise to DYT1 dystonia.

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Local translation in neuronal processes

Cited by 107 publications

References 77 publications

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

FMRP binding to a ranked subset of long genes is revealed by coupled CLIP and TRAP in specific neuronal cell types

Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene

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