Monosomes actively translate synaptic mRNAs in neuronal processes

Biever, Anne; Glock, Caspar; Tushev, Georgi; Ciirdaeva, Elena; Langer, Julian D.; Schuman, Erin M.

doi:10.1101/687475

Cited by 43 publications

(65 citation statements)

References 64 publications

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“…However, very few polysomes have been observed in neuronal processes and monosomes are most populous in these compartments. Consistent with their high numbers, monosomes were shown to be important sources of translation in neuronal processes requiring protein production, as well as in synapses 54 . Further analysis revealed that certain transcripts show strong preferences for translation by either polysomes or monosomes.…”

Section: Rna Localization and Local Translation In Neuronsmentioning

confidence: 82%

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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: Rna Localization and Local Translation In Neuronsmentioning

confidence: 82%

“…To tackle the first question, Biever et al used a ribosome footprinting approach to produce an unbiased list of mRNAs undergoing active translation in neuronal processes in vivo 54 . Similar to Cajigas et al, they isolated hippocampal neuropils containing both axons and dendrites.…”

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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“…It is widely accepted that actively translating mRNAs bind multiple ribosomes. However, this is contradicted by recent findings that translation occurs also on mRNAs bound to monosomes, and that translation is not directly proportional to the number of ribosomes on mRNA ( Requião et al, 2017 ; Neidermyer and Whelan, 2019 ; Biever et al, 2020 ). Relative to standard linear gradient of polysome profiling, non-linear gradients of RNC-seq (full-length translating mRNA sequencing) enable translating mRNAs elution at smaller volumes to circumvent the limitations of polysome profiling ( Liang et al, 2018 ).…”

Section: Narrow Sense Translatomicsmentioning

confidence: 68%

“…Despite evidence indicating that mature axons are capable of protein synthesis ( Kalinski et al, 2015 ; Rangaraju et al, 2017 ), the small size of axons and tight connections with glia and post-synapses have made in vivo transcriptome and translatome isolation extremely challenging. Importantly, microdissection-based approaches are limited to brain regions (e.g., the hippocampus; ( Biever et al, 2020 ) where axons are in separable lamina. While abundant transcriptome analysis demonstrated that the mRNAs for cAMP-response element binding protein (CREB), Na v 1.8, and other ion channels localize to DRG axons in vitro ( Thakor et al, 2009 ; Melemedjian et al, 2014 ; Hirai et al, 2017 ), there are technological challenges to research in which mRNAs are translated locally in nociceptor axons in vivo .…”

Section: Narrow Sense Translatomicsmentioning

confidence: 99%

Insights Into Translatomics in the Nervous System

et al. 2020

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Most neurological disorders are caused by abnormal gene translation. Generally, dysregulation of elements involved in the translational process disrupts homeostasis in neurons and neuroglia. Better understanding of how the gene translation process occurs requires detailed analysis of transcriptomic and proteomic profile data. However, a lack of strictly direct correlations between mRNA and protein levels limits translational investigation by combining transcriptomic and proteomic profiling. The much better correlation between proteins and translated mRNAs than total mRNAs in abundance and insufficiently sensitive proteomics approach promote the requirement of advances in translatomics technology. Translatomics which capture and sequence the mRNAs associated with ribosomes has been effective in identifying translational changes by genetics or projections, ribosome stalling, local translation, and transcript isoforms in the nervous system. Here, we place emphasis on the main three translatomics methods currently used to profile mRNAs attached to ribosome-nascent chain complex (RNC-mRNA). Their prominent applications in neurological diseases including glioma, neuropathic pain, depression, fragile X syndrome (FXS), neurodegenerative disorders are outlined. The content reviewed here expands our understanding on the contributions of aberrant translation to neurological disease development.

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“…According to literature, we found that both CHX and sBlock are able to stabilize AHA-peptides on ribosomes and polysomes (i.e. actively translating complexes) (Biever et al, 2020; Mathias et al, 1964). The efficiency to anchor polypeptides on ribosomes in CHX and sBlock treated cells was 50% higher compared to untreated cells, confirming that the drugs effectively stabilize nascent polypeptides (Fig.…”

Section: Resultsmentioning

confidence: 88%

One-shot analysis of translated mammalian lncRNAs with AHARIBO

Minati¹,

Firrito²,

Piano³

et al. 2020

Preprint

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SUMMARYA vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode uncharacterized proteins, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated lncRNAs and peptide-producing lncRNAs.Here we present AHARIBO, a method for the detection of lncRNAs either untranslated, but associated with ribosomes, or encoding small peptides. Using AHARIBO in mouse embryonic stem cells during neuronal differentiation, we isolated ribosome-protected RNA fragments, translated RNAs and corresponding de novo synthesized polypeptides. Besides identifying mRNAs under active translation and associated ribosomes, we found and distinguished lncRNAs acting as ribosome sponges or encoding micropeptides, laying the ground for a better functional understanding of hundreds lncRNAs.

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Monosomes actively translate synaptic mRNAs in neuronal processes

Cited by 43 publications

References 64 publications

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

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

Insights Into Translatomics in the Nervous System

One-shot analysis of translated mammalian lncRNAs with AHARIBO

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