Tissue-Specific Regulation of Translational Readthrough Tunes Functions of the Traffic Jam Transcription Factor

Karki, Prajwal; Carney, Travis D.; Maracci, Cristina; Yatsenko, Andriy S.; Shcherbata, Halyna R.; Rodnina, Marina V.

doi:10.1101/2020.12.04.411694

Cited by 7 publications

(4 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possibility is translational readthrough (63)(64)(65)(66)(67), or alternatively the bacteria could be inserting selenocysteine into these proteins in lieu of the stop codon. dgcQ mutations have been observed in at least six different strains of EAEC in the same specific pattern observed in S. flexneri 2457T, with an insertion of stop codon at 312 amino acid position and adjacent methionine (AUG) at 314 codon; this suggests that, like dgcE, the dgcQ adaptation is not unique to this specific Shigella strain (62).…”

Section: Discussionmentioning

confidence: 99%

Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP

Ojha,

Krug,

Jones

et al. 2024

Preprint

View full text Add to dashboard Cite

The intracellular human pathogenShigellainvades the colonic epithelium to cause disease. Prior to invasion, this bacterium navigates through different environments within the human body, including the stomach and the small intestine. To adapt to changing environments,Shigellauses the bacterial second messenger c-di-GMP signaling system, synthesized by diguanylate cyclases (DGCs) encoding GGDEF domains.Shigella flexneriencodes a total of 9 GGDEF or GGDEF-EAL domain enzymes in its genome, but 5 of these genes have acquired mutations that presumably inactivated the c-di-GMP synthesis activity of these enzymes. In this study, we examined individualS. flexneriDGCs for their role in c-di-GMP synthesis and pathogenesis. We individually expressed each of the 4 intact DGCs in anS. flexneristrain where these 4 DGCs had been deleted (Δ4DGC). We found that the 4S. flexneriintact DGCs synthesize c-di-GMP at different levelsin vitroand during infection of tissue-cultured cells. We also found thatdgcFanddgcIexpression significantly reduces invasion and plaque formation, anddgcFexpression increases acid sensitivity, and that these phenotypes did not correspond with measured c-di-GMP levels. However, deletion of these 4 DGCs did not eliminateS. flexneric-di-GMP, and we found thatdgcE, dgcQ,anddgcN, which all have nonsense mutations prior to the GGDEF domain, still produce c-di-GMP. TheseS. flexneridegenerate DGC genes are expressed as multiple proteins, consistent with multiple start codons within the gene. We propose that both intact and degenerate DGCs contribute toS. flexneric-di-GMP signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP

Ojha,

Krug,

Jones

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, we found ribosome footprints also on the 3′ UTR of certain transcripts, such as Synapsin (Figure 3C). Stop-codon readthrough has been reported to be more frequent in neurons than in other cell types (49)(50)(51). Because the readthrough events extend the protein C-terminus, its regulation can add yet another layer of cell-type diversity (14,52,53).…”

Section: Discussionmentioning

confidence: 99%

Translational regulation enhances distinction of cell types in the nervous system

Ichinose

Kondo

Kanno

et al. 2023

Preprint

View full text Add to dashboard Cite

Multicellular organisms are composed of specialized cells with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains to be understood. By performing RNA-seq and Ribo-seq from genetically labelled cell types in Drosophila, we profiled the transcriptome and translatome of neuronal and glial cells in the brain. This comparative profiling revealed substantial posttranscriptional regulation of protein expression. We further found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low especially in glia, leading to preferential translation in neurons. Notably, the distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5′ untranslated regions (UTR) in glial cells. Using a transgenic reporter system, we provide evidence that the UTR confer translational suppression selectively in glia. Overall, these findings underscore the profound impact of translational regulation in shaping cell identity and provide new insights into the molecular mechanisms driving cell-type diversity.

show abstract

“…Recently, studies involving Ribo-Seq of animal tissues and organs revealed organspecific differences in translation efficiency and elongation speed [12][13][14][15]. Other findings revealed different tRNA repertoires and codon usage in different tissues [16,17], as well as peculiar features like readthrough rate [18]. However, to which extent the tissue-specificity of gene expression is determined at the translation level is still a poorly resolved issue.…”

Section: Recentmentioning

confidence: 99%

Human tissues exhibit diverse composition of translation machinery

Anisimova

Kolyupanova

Makarova

et al. 2023

Preprint

View full text Add to dashboard Cite

While protein synthesis is vital for the majority of cell types of the human body, diversely differentiated cells require specific translation regulation. This suggests specialization of translation machinery across tissues and organs. Using transcriptomic data from GTEx, FANTOM, and Gene Atlas we systematically explored the abundance of transcripts encoding translation factors and aminoacyl-tRNA synthetases (ARSases) in human tissues. We revised a few known and identified several novel translation-related genes exhibiting strict tissue-specific expression. The proteins they encode include eEF1A1, eEF1A2, PABPC1L, PABPC3, eIF1B, eIF4E1B, eIF4ENIF1, and eIF5AL1. Furthermore, our analysis revealed a pervasive tissue-specific relative abundance of translation machinery components (e.g. PABP and eRF3 paralogs, eIF2B subunits, eIF5MPs, and some ARSases), suggesting presumptive variance in the composition of translation initiation, elongation, and termination complexes. These conclusions were largely confirmed by the analysis of proteomic data. Finally, we paid attention to sexual dimorphism in the repertoire of translation factors encoded in sex chromosomes (eIF1A, eIF2γ, and DDX3), and identified testis and brain as organs with the most diverged expression of translation-associated genes.

show abstract

Tissue-Specific Regulation of Translational Readthrough Tunes Functions of the Traffic Jam Transcription Factor

Cited by 7 publications

References 96 publications

Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP

Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP

Translational regulation enhances distinction of cell types in the nervous system

Human tissues exhibit diverse composition of translation machinery

Contact Info

Product

Resources

About