Human Tissues Exhibit Diverse Composition of Translation Machinery

Anisimova, Aleksandra S.; Kolyupanova, Natalia M; Makarova, Nadezhda E.; Egorov, Artyom A.; Kulakovskiy, Ivan V.; Dmitriev, Sergey E.

doi:10.3390/ijms24098361

Cited by 7 publications

(1 citation statement)

References 117 publications

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“…In contrast, for Huh7 samples, efficiency at this start is much lower, and consequently, the CDS translon is predominant. The reasons for these cell-specific differences are beyond the scope of this work, but several mechanisms may be responsible, including different levels of translation factors that recognize translation initiation starts ( Anisimova et al 2023 ).…”

Section: Implementations Of Rdgsmentioning

confidence: 99%

Ribosome decision graphs for the representation of eukaryotic RNA translation complexity

Tierney,

Świrski,

Tjeldnes

et al. 2024

Genome Res.

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The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, within both annotated protein-coding and noncoding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term ribosome decision graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the latter “translons.” Nondeterministic events, such as initiation, reinitiation, selenocysteine insertion, or ribosomal frameshifting, are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions and for analyzing genetic variation and quantitative genome-wide data on translation for characterization of regulatory modulators of translation.

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Section: Implementations Of Rdgsmentioning

confidence: 99%

Ribosome decision graphs for the representation of eukaryotic RNA translation complexity

Tierney,

Świrski,

Tjeldnes

et al. 2024

Genome Res.

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Deciphering the role of sphingolipid metabolism in the immune microenvironment and prognosis of esophageal cancer via single-cell sequencing and bulk data analysis

He,

Tang,

Lai

et al. 2024

Discov Onc

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Monitoring integrated stress response in liveDrosophila

Lidsky

Yuan

Lashkevich

et al. 2023

Preprint

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Cells exhibit stress responses to various environmental changes. Among these responses, the integrated stress response (ISR) plays a pivotal role as a crucial stress signaling pathway. While extensive ISR research has been conducted on cultured cells, our understanding of its implications in multicellular organisms remains limited, largely due to the constraints of current techniques that hinder our ability to track and manipulate the ISR in vivo. To overcome these limitations, we have successfully developed an internal ribosome entry site (IRES)-based fluorescent reporter system. This innovative reporter enables us to label Drosophila cells, within the context of a living organism, that exhibit eIF2 phosphorylation-dependent translational shutoff- a characteristic feature of the ISR and viral infections. Through this methodology, we have unveiled tissue- and cell-specific regulation of stress response in Drosophila flies and have even been able to detect stressed tissues in vivo during virus and bacterial infections. To further validate the specificity of our reporter, we have engineered ISR-null eIF2α-S50A mutant flies for stress response analysis. Our results shed light on the tremendous potential of this technique for investigating a broad range of developmental, stress, and infection-related experimental conditions. Combining the reporter tool with ISR-null mutants establishes Drosophila as an exceptionally powerful model for studying the ISR in the context of multicellular organisms.

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Human Tissues Exhibit Diverse Composition of Translation Machinery

Cited by 7 publications

References 117 publications

Ribosome decision graphs for the representation of eukaryotic RNA translation complexity

Ribosome decision graphs for the representation of eukaryotic RNA translation complexity

Deciphering the role of sphingolipid metabolism in the immune microenvironment and prognosis of esophageal cancer via single-cell sequencing and bulk data analysis

Monitoring integrated stress response in liveDrosophila

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