A Solitary Stalled 80S Ribosome Prevents mRNA Recruitment to Stress Granules DOI Creative Commons

Artem G. Fedorovskiy,

Anton V. Burakov, Ilya M. Terenin

et al.

Biochemistry (Moscow), Journal Year: 2023, Volume and Issue: 88(11), P. 1786 - 1799

Published: Nov. 1, 2023

In response to stress stimuli, eukaryotic cells typically suppress protein synthesis. This leads the release of mRNAs from polysomes, their condensation with RNA-binding proteins, and formation non-membrane-bound cytoplasmic compartments called granules (SGs). SGs contain 40S but generally lack 60S ribosomal subunits. It is known that cycloheximide, emetine, anisomycin, ribosome inhibitors block progression 80S ribosomes along mRNA stabilize prevent SG assembly. Conversely, puromycin, which induces premature termination, releases polysomes stimulates SGs. The same effect caused by some translation initiation inhibitors, lead polysome disassembly accumulation in form stalled 48S preinitiation complexes. Based on these other data, it believed trigger for presence extended ribosome-free segments, tend condensates cell. this study, we evaluated ability various small-molecule or stimulate assembly under conditions severe oxidative induced sodium arsenite. Contrary expectations, found ribosome-targeting elongation a specific type, arrest solitary at beginning coding regions do not interfere all subsequent completing leaving transcripts (such as harringtonine, lactimidomycin, T-2 toxin), completely arsenite-induced These observations suggest even single sufficient its recruitment into SGs, formation. We propose entry may be mediated contacts between proteins those subunits remain inaccessible when are associated.

Language: Английский

Non-Canonical Translation Initiation Mechanisms Employed by Eukaryotic Viral mRNAs DOI Open Access
Ivan I. Sorokin,

Konstantin S. Vassilenko,

Ilya M. Terenin

et al.

Biochemistry (Moscow), Journal Year: 2021, Volume and Issue: 86(9), P. 1060 - 1094

Published: Sept. 1, 2021

Language: Английский

Citations

44
Regulation and outcomes of localized RNA translation DOI Creative Commons
Alexander N. Gasparski, Devon E. Mason, Konstadinos Moissoglu

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2022, Volume and Issue: 13(6)

Published: Feb. 14, 2022

Spatial segregation of mRNAs in the cytoplasm cells is a well-known biological phenomenon that widely observed diverse species spanning different kingdoms life. In mammalian cells, localization has been documented and studied quite extensively highly polarized most notably neurons, where localized function to direct protein production at sites are distant from soma. Recent studies have strikingly revealed large proportion cellular transcriptome exhibits distributions even lack an obvious need for long-range transport, such as fibroblasts or epithelial cells. This review focuses on emerging concepts regarding functional outcomes mRNA targeting We also discuss regulatory mechanisms controlling these events, with emphasis role cell mechanics organization cytoskeleton. article categorized under: Translation > Regulation RNA Export Localization Localization.

Language: Английский

Citations

31
Cell death or survival: Insights into the role of mRNA translational control DOI Creative Commons
Nupur Bhatter, Sergey E. Dmitriev, Pavel Ivanov

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 138 - 154

Published: June 24, 2023

Language: Английский

Citations

22
Mitochondrial phosphoproteomes are functionally specialized across tissues DOI Creative Commons
Fynn M. Hansen, Laura S. Kremer, Özge Karayel

et al.

Life Science Alliance, Journal Year: 2023, Volume and Issue: 7(2), P. e202302147 - e202302147

Published: Nov. 20, 2023

Mitochondria are essential organelles whose dysfunction causes human pathologies that often manifest in a tissue-specific manner. Accordingly, mitochondrial fitness depends on versatile proteomes specialized to meet diverse requirements. Increasing evidence suggests phosphorylation may play an important role regulating functions and pathophysiology. Building recent advances mass spectrometry (MS)-based proteomics, we here quantitatively profile tissue along with their matching phosphoproteomes. We isolated mitochondria from mouse heart, skeletal muscle, brown adipose tissue, kidney, liver, brain, spleen by differential centrifugation followed separation Percoll gradients performed high-resolution MS analysis of the This in-depth map substantially quantifies known predicted proteins provides resource core ( mitophos.de ). Predicting kinase substrate associations for different compartments indicates regulation at phosphoproteome level. Illustrating functional value our resource, reproduce events dynamin-related protein 1 responsible its recruitment fission initiation describe clusters MIGA2 linked fusion.

Language: Английский

Citations

21
The kinesin-3 KIF1C undergoes liquid-liquid phase separation for accumulation of specific transcripts at the cell periphery DOI Creative Commons
Qi Geng, Jakia Jannat Keya, Takashi Hotta

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(15), P. 3192 - 3213

Published: June 19, 2024

Language: Английский

Citations

7
Ribosomal control in RNA virus-infected cells DOI Creative Commons
Xiao Wang, Jie Zhu, Da Zhang

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 7, 2022

Viruses are strictly intracellular parasites requiring host cellular functions to complete their reproduction cycle involving virus infection of cell, viral genome replication, protein translation, and virion release. Ribosomes synthesis factories in cells, viruses need manipulate ribosomes synthesis. use translation initiation factors through own RNA structures or cap structures, thereby inducing synthesize proteins. also affect ribosome production the assembly mature ribosomes, regulate recognition mRNA by promoting inhibiting antiviral immune Here, we review remarkable mechanisms used particular, which induce formation specific heterogeneous required for translation. This provides valuable insights into control diseases from perspective

Language: Английский

Citations

26
Advancement in the development of mRNA‐based vaccines for respiratory viruses DOI Open Access

Tays Troncoso‐Bravo,

Mario A. Ramírez, Ricardo A. Loaiza

et al.

Immunology, Journal Year: 2024, Volume and Issue: 173(3), P. 481 - 496

Published: Aug. 19, 2024

Acute respiratory infections are the leading cause of death and illness in children under 5 years old represent a significant burden older adults. Primarily caused by viruses infecting lower tract, symptoms include cough, congestion, low-grade fever, potentially to bronchiolitis pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines biopharmaceutical formulations that employ mRNA molecules induce specific immune responses, facilitating expression viral or bacterial antigens promoting immunization against infectious diseases. Notably, this technology had relevance during COVID-19 pandemic, as these helped limit SARS-CoV-2 virus infections, hospitalizations, deaths. Importantly, promise be implemented new alternatives for fighting other viruses, such influenza, human syncytial virus, metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, implications viruses.

Language: Английский

Citations

5
Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus DOI Creative Commons
Zaur M. Kachaev, Sergey D. Ivashchenko, Eugene Kozlov

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3239 - 3239

Published: Nov. 19, 2021

Components of the translation apparatus, including ribosomal proteins, have been found in cell nuclei various organisms. apparatus are involved nuclear processes, particularly those associated with genome integrity control and stages gene expression, such as transcription, mRNA processing, export. intranuclear trafficking; import export RNA proteins; regulate activity, stability, functional recruitment proteins. The translocation these components is often response to stimulation stress, addition playing critical roles oncogenesis viral infection. Many moonlighting integral stress coupling expression subprocesses. Thus, this phenomenon represents a significant interest for both basic applied molecular biology. Here, we provide an overview current data regarding functions factors proteins nucleus.

Language: Английский

Citations

32
Understanding circadian regulation of mammalian cell function, protein homeostasis, and metabolism DOI Creative Commons
Alessandra Stangherlin, Estere Seinkmane, John S. O’Neill

et al.

Current Opinion in Systems Biology, Journal Year: 2021, Volume and Issue: 28, P. 100391 - 100391

Published: Oct. 8, 2021

Circadian rhythms are ∼24 h cycles of organismal and cellular activity ubiquitous to mammalian physiology. A prevailing paradigm suggests that timing information flows linearly from rhythmic transcription via protein abundance changes drive circadian regulation function. Challenging this view, recent evidence indicates daily variation in many functions arises through post-translational activity. We suggest primarily maintain proteome homeostasis rather than perturb it. Indeed, although relevant timekeeping mechanism, clock may be the exception, not rule. Informed by insights yeast models, we propose optimal bioenergetic efficiency results coupled target rapamycin complex activity, synthesis/turnover, ion transport sequestration, which facilitatory metabolic flux substrate utilisation. Such consolidation renewal would account for aspects cell biology whilst maintaining osmotic homeostasis.

Language: Английский

Citations

31
Relocalization of Translation Termination and Ribosome Recycling Factors to Stress Granules Coincides with Elevated Stop-Codon Readthrough and Reinitiation Rates upon Oxidative Stress DOI Creative Commons

Desislava S. Makeeva,

Claire L. Riggs, Anton V. Burakov

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 259 - 259

Published: Jan. 8, 2023

Upon oxidative stress, mammalian cells rapidly reprogram their translation. This is accompanied by the formation of stress granules (SGs), cytoplasmic ribonucleoprotein condensates containing untranslated mRNA molecules, RNA-binding proteins, 40S ribosomal subunits, and a set translation initiation factors. Here we show that arsenite-induced causes dramatic increase in stop-codon readthrough rate significantly elevates reinitiation levels on uORF-containing bicistronic mRNAs. We also report recruitment termination factors eRF1 eRF3, as well ribosome recycling ABCE1, eIF2D, MCT-1, DENR to SGs upon arsenite treatment. Localization these may contribute rapid resumption after relief SG disassembly. It suggest presence post-termination, recycling, or complexes SGs. new layer translational control under conditions, relying altered spatial distribution between cellular compartments, discussed.

Language: Английский

Citations

11