High-Resolution Native Mass Spectrometry

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(8), P. 7269 - 7326

Published: Aug. 20, 2021

Native mass spectrometry (MS) involves the analysis and characterization of macromolecules, predominantly intact proteins protein complexes, whereby as much possible native structural features analytes are retained. As such, MS enables study secondary, tertiary, even quaternary structure other biomolecules. represents a relatively recent addition to analytical toolbox has over past decade experienced immense growth, especially in enhancing sensitivity resolving power but also ease use. With advent dedicated analyzers, sample preparation separation approaches, targeted fragmentation techniques, software solutions, number practitioners novel applications risen both academia industry. This review focuses on developments, particularly high-resolution MS, describing assemblies, proteoform profiling of─among others─biopharmaceuticals plasma proteins, quantitative qualitative protein-ligand interactions, with latter covering lipid, drug, carbohydrate molecules, name few.

Language: Английский

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Intracellular mRNA transport and localized translation

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(7), P. 483 - 504

Published: April 9, 2021

Language: Английский

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Monosomes actively translate synaptic mRNAs in neuronal processes

Science, Journal Year: 2020, Volume and Issue: 367(6477)

Published: Jan. 31, 2020

To accommodate their complex morphology, neurons localize messenger RNAs (mRNAs) and ribosomes near synapses to produce proteins locally. However, a relative paucity of polysomes (considered the active sites translation) detected in electron micrographs neuronal processes has suggested limited capacity for local protein synthesis. In this study, we used polysome profiling together with ribosome footprinting microdissected rodent synaptic regions reveal surprisingly high number dendritic and/or axonal transcripts preferentially associated monosomes (single ribosomes). Furthermore, were process Most mRNAs showed similar translational status cell bodies neurites, but some exhibited differential occupancy compartments. Monosome-preferring often encoded high-abundance proteins. Thus, monosome translation contributes proteome.

Language: Английский

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Sperm RNA code programmes the metabolic health of offspring

Nature Reviews Endocrinology, Journal Year: 2019, Volume and Issue: 15(8), P. 489 - 498

Published: June 24, 2019

Language: Английский

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PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(4), P. 424 - 436

Published: April 1, 2021

Language: Английский

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Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance

Cancer Research, Journal Year: 2022, Volume and Issue: 82(13), P. 2344 - 2353

Published: March 18, 2022

Abstract Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is multistep process begins in the nucleolus concludes cytoplasm. The tightly controlled by multiple checkpoint surveillance pathways. Perturbations these checkpoints pathways can lead to hyperactivation ribosome biogenesis. Emerging evidence suggests cancer cells harbor specialized class ribosomes (onco-ribosomes) facilitates oncogenic program, modulates cellular functions, promotes metabolic rewiring. Mutations proteins, processing, assembly factors result ribosomopathies associated with an increased risk developing malignancies. Recent studies have linked mutations aberrant poor prognosis, highlighting ribosome-targeted therapy promising approach for treating patients cancer. Here, we summarize various aspects dysregulation impact resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, clinical outcome. target, understanding important determinants this will allow improved perhaps selective strategies target biosynthesis.

Language: Английский

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Hallmarks of ribosomopathies

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 48(3), P. 1013 - 1028

Published: July 12, 2019

Ribosomopathies are diseases caused by defects in ribosomal constituents or factors with a role ribosome assembly. Intriguingly, congenital ribosomopathies display paradoxical transition from early symptoms due to cellular hypo-proliferation an elevated cancer risk later life. Another association between and came into view after the recent discovery of somatic mutations proteins rDNA copy number changes variety tumor types, giving rise ribosomopathies. Despite these clear connections cancer, molecular mechanisms which this essential machinery oncogenic only start emerge. In review, impact on function their promoting oncogenesis described. particular, we discuss emerging hallmarks such as appearance 'onco-ribosomes' that specialized translating oncoproteins, dysregulation translation-independent extra-ribosomal functions proteins, rewired protein energy metabolism, extensive oxidative stress leading DNA damage. We end integrating findings model can provide explanation how could lead hypo- hyper-proliferation bone marrow failure syndromes risk.

Language: Английский

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Ribosomopathies: Old Concepts, New Controversies

Trends in Genetics, Journal Year: 2019, Volume and Issue: 35(10), P. 754 - 767

Published: July 31, 2019

Language: Английский

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Origins and evolving functionalities of tRNA-derived small RNAs

Trends in Biochemical Sciences, Journal Year: 2021, Volume and Issue: 46(10), P. 790 - 804

Published: May 27, 2021

Language: Английский

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Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 21, 2021

Abstract Owing to their morphological complexity and dense network connections, neurons modify proteomes locally, using mRNAs ribosomes present in the neuropil (tissue enriched for dendrites axons). Although ribosome biogenesis largely takes place nucleus perinuclear region, neuronal ribosomal protein (RP) have been frequently detected remotely, axons. Here, imaging profiling, we directly RP translation neuropil. Combining brief metabolic labeling with mass spectrometry, found that a group of RPs rapidly associated translating cytoplasm this incorporation was independent canonical biogenesis. Moreover, probability some regulated by location (neurites vs. cell bodies) changes cellular environment (following oxidative stress). Our results suggest new mechanisms local activation, repair and/or specialization translational machinery within processes, potentially allowing synapses rapid means regulate synthesis.

Language: Английский

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