The brain's dark transcriptome: Sequencing RNA in distal compartments of neurons and glia DOI Creative Commons
Seth A. Ament, Alexandros Poulopoulos

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102725 - 102725

Published: May 15, 2023

Transcriptomic approaches are powerful strategies to map the molecular diversity of cells in brain. Single-cell genomic atlases have now been compiled for entire mammalian brains. However, complementary techniques only just beginning subcellular transcriptomes from distal cellular compartments. We review single-cell datasets alongside subtranscriptome data brain explore development and diversity. discuss how RNA-seq misses transcripts localized away cell bodies, which form 'dark transcriptome' brain: a collection subtranscriptomes dendrites, axons, growth cones, synapses, endfeet with important roles function. Recent advances transcriptome sequencing reveal these elusive pools RNA. outline success stories date uncovering constituent neurons glia, as well present emerging toolkit that is accelerating pace discovery.

Language: Английский

De-centralizing the Central Dogma: mRNA translation in space and time DOI Creative Commons
Ashley M. Bourke, Andre Schwarz, Erin M. Schuman

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(3), P. 452 - 468

Published: Jan. 19, 2023

As our understanding of the cell interior has grown, we have come to appreciate that most cellular operations are localized, is, they occur at discrete and identifiable locations or domains. These domains contain enzymes, machines, other components necessary carry out regulate these localized operations. Here, review features one such operation: localization translation mRNAs within subcellular compartments observed across types organisms. We describe conceptual advantages "ingredients" mechanisms local translation. focus on nature mRNAs, how travel get this process is regulated. also evaluate current protein synthesis machines (ribosomes) their cadre regulatory elements, factors.

Language: Английский

Citations

55
Chaperone-directed ribosome repair after oxidative damage DOI Open Access

Yoon-Mo Yang,

Young‐Eun Jung, Daniel Abegg

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(9), P. 1527 - 1537.e5

Published: April 21, 2023

Language: Английский

Citations

47
mRNA stability and m6A are major determinants of subcellular mRNA localization in neurons DOI Creative Commons
Inga Loedige, Artem Baranovskii, Samantha Mendonsa

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(15), P. 2709 - 2725.e10

Published: July 13, 2023

For cells to perform their biological functions, they need adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model mRNA localization involves sequences called "zipcodes" that direct proper locations. However, while thousands localize cells, only a few zipcodes have been identified, suggesting additional mechanisms contribute localization. Here, we assess role stability by combining isolation soma neurites mouse primary cortical mESC-derived neurons, SLAM-seq, m6A-RIP-seq, perturbation destabilization mechanisms, analysis multiple datasets. We show depletion elements, such as m6A, AU-rich suboptimal codons, functions mechanism mediates associated with housekeeping several types neurons.

Language: Английский

Citations

46
The Trail of axonal protein Synthesis: Origins and current functional Landscapes DOI
Joaquín Garat, Andrés Di Paolo, Guillermo Eastman

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Subcellular and regional localization of mRNA translation in midbrain dopamine neurons DOI Creative Commons
Benjamin D. Hobson, Linghao Kong,

María Florencia Angelo

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(2), P. 110208 - 110208

Published: Jan. 1, 2022

Midbrain dopaminergic (mDA) neurons exhibit extensive dendritic and axonal arborizations, but local protein synthesis is not characterized in these neurons. Here, we investigate messenger RNA (mRNA) localization translation mDA neuronal axons dendrites, both of which release dopamine (DA). Using highly sensitive ribosome-bound sequencing imaging approaches, find no evidence for mRNA axons. In contrast, dendrites the substantia nigra pars reticulata (SNr) contain ribosomes mRNAs encoding major components DA synthesis, release, reuptake machinery. Surprisingly, also observe synaptic vesicle-related proteins, including those involved exocytic fusion. Our results are consistent with a role regulation from translatome data define molecular signature sparse SNr, enrichment Atp2a3/SERCA3, an atypical ER calcium pump.

Language: Английский

Citations

41
Massively parallel identification of mRNA localization elements in primary cortical neurons DOI Creative Commons
Samantha Mendonsa, Nicolai von Kügelgen,

Sayaka Dantsuji

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 16, 2023

Abstract Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of mRNAs specific areas, where they are translated into proteins with local functions. This mRNA is mediated by cis -regulatory elements mRNAs, commonly called ‘zipcodes’. Although there hundreds localized only a few zipcodes have been characterized. Here we describe novel neuronal zipcode identification protocol (N-zip) that can identify across 3′ untranslated regions. approach combines method separating principal neurons—cell bodies neurites—with massively parallel reporter assay. N-zip identifies let-7 binding site (AU) n motif as de novo mouse primary cortical neurons. Our analysis also provides, our knowledge, first demonstration an miRNA affecting suggests strategy for detecting more zipcodes.

Language: Английский

Citations

36
Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions DOI Creative Commons
Sophia Häfner, Martin Jansson, Kübra Altinel

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(17), P. 1593 - 1609.e9

Published: July 19, 2023

Language: Английский

Citations

35
An abundance of free regulatory (19 S ) proteasome particles regulates neuronal synapses DOI
Chao Sun,

Kristina Desch,

Belquis Nassim-Assir

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6647)

Published: May 25, 2023

The proteasome, the major protein-degradation machine in cells, regulates neuronal synapses and long-term information storage. Here, using super-resolution microscopy, we found that two essential subcomplexes of regulatory (19S) catalytic (20S) particles, are differentially distributed within individual rat cortical neurons. We discovered an unexpected abundance free 19S particles near synapses. bind deubiquitylate lysine 63-ubiquitin (Lys63-ub), a non-proteasome-targeting ubiquitin linkage. Pull-down assays revealed significant overrepresentation synaptic molecules as Lys63-ub interactors. Inhibition deubiquitylase activity significantly altered excitatory transmission reduced availability AMPA receptors at multiple trafficking points proteasome-independent manner. Together, these results reveal moonlighting function proteasomal subcomplex

Language: Английский

Citations

29
Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis DOI Creative Commons
Diana Piol,

Tessa Robberechts,

Sandrine Da Cruz

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(9), P. 1355 - 1380

Published: March 23, 2023

Language: Английский

Citations

26
Specialized Ribosomes in Health and Disease DOI Open Access
Sarah Miller, Clinton C. MacDonald, Morgana K. Kellogg

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6334 - 6334

Published: March 28, 2023

Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or changes ribosome that regulate translation a group transcripts. These alterations have been shown affect affinity ribosomes for certain mRNAs change cotranslational folding nascent polypeptides exit tunnel. The identification requires incorporation ribosomal proteins modifications rRNA and/or protein lead(s) physiologically relevant translation. In this review, we summarize specialization mammals discuss their relevance several human diseases.

Language: Английский

Citations

24