5' Untranslated regions tune Toxoplasma translation [MPRA]
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PROVIDER: PRJNA1288538 | ENA |
REPOSITORIES: ENA
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Project description:5' Untranslated regions tune Toxoplasma translation [Ribosome Profiling]
| PRJNA1288540 | ENA
Project description:Some of the longest 5′ untranslated regions (UTRs) documented in eukaryotes belong to parasites of the phylum Apicomplexa. Translational regulation plays prominent roles in the development of these parasites, including the agents of toxoplasmosis (Toxoplasma gondii) and malaria. To understand the function of 5′ UTRs in apicomplexan translation, we performed high-resolution ribosome profiling of T. gondii in human fibroblasts. We show that parasite translation efficiency (TE) is largely controlled by 5′ UTR features and tuned by the number of upstream AUGs (uAUGs). Examination of ribosome occupancy reveals that, despite widespread engagement of uAUGs, parasite ribosomes seldom translate uORFs. These features are reaffirmed in a massively parallel reporter assay examining the effect of more than 30,000 synthetic 5′ UTRs in T. gondii. A model trained on these results accurately predicted the TE of newly designed 5′ UTRs. Together, this work defines the regulatory language of T. gondii translation, providing a framework to understand the evolution of exceptionally long 5′ UTRs in apicomplexans.
2025-07-15 | GSE302108 | GEO
Project description:Some of the longest 5′ untranslated regions (UTRs) documented in eukaryotes belong to parasites of the phylum Apicomplexa. Translational regulation plays prominent roles in the development of these parasites, including the agents of toxoplasmosis (Toxoplasma gondii) and malaria. To understand the function of 5′ UTRs in apicomplexan translation, we performed high-resolution ribosome profiling of T. gondii in human fibroblasts. We show that parasite translation efficiency (TE) is largely controlled by 5′ UTR features and tuned by the number of upstream AUGs (uAUGs). Examination of ribosome occupancy reveals that, despite widespread engagement of uAUGs, parasite ribosomes seldom translate uORFs. These features are reaffirmed in a massively parallel reporter assay examining the effect of more than 30,000 synthetic 5′ UTRs in T. gondii. A model trained on these results accurately predicted the TE of newly designed 5′ UTRs. Together, this work defines the regulatory language of T. gondii translation, providing a framework to understand the evolution of exceptionally long 5′ UTRs in apicomplexans.
2025-07-15 | GSE302107 | GEO
Project description:Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.
| S-EPMC11317171 | biostudies-literature
Project description:Peptides encoded by 5’ untranslated regions mediate pain sensitization
| PRJNA480907 | ENA
Project description:Nociceptors are neurons responsible for the detection of pain producing stimuli. Persistent changes in their activity, termed plasticity, benefit survival through injury avoidance and are regulated on a translational basis. Yet, the mRNAs whose translation facilitates plasticity are unknown. Here, we apply ribosome profiling to dorsal root ganglion and identify a small number of transcripts that are selectively translated in response to plasticity mediators. Among them are Arc and Fos, genes implicated in episodic learning in the brain. We demonstrate that the ribosomal S6 kinase 1 is responsible for their production in nociceptors. Blocking S6 driven translation also reduces pain associated behavioral responses in vivo. In addition to translation of coding regions of mRNA, we detect pervasive ribosome occupancy in 5’ untranslated regions. We find that peptides encoded by open reading frames in the 5’ untranslated regions of Calca and Egr2 increase neuronal excitability in vitro and are sufficient to induce pain-like behaviors in vivo. Together, our findings uncover new targets of translational control that drive changes in plasticity and suggest new mechanisms for targeted pain therapeutics that disrupt pain signaling.
2020-02-01 | GSE117043 | GEO
Project description:Homo sapiens and Macaca fascicularis neural progenitor cell lines were transduced with a lentiviral MPRA (Massively Parallel Reporter Assay) library. MPRA barcode sequencing and RNA-seq was performed on the extracted RNA. MPRA data was used to compare activity of regulatory sequences across 75 mammalian species with a focus on primates and correlate these activities with the Phenotype of gyrencephaly.
2021-05-12 | E-MTAB-9952 | biostudies-arrayexpress
Project description:Toxoplasma gondii persists in humans by converting from actively replicating acute stage tachyzoites to slow-growing chronic stage bradyzoites. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a chemical mutagenesis screen, we identified translation initiation factor eIF1.2 as being critical for T. gondii differentiation. The presence of an F97L mutation in eIF1.2 identified in the screen or the complete lack eIF1.2 (∆eIF1.2) markedly impeded bradyzoite cyst formation in culture and in the brains of infected mice. ∆eIF1.2 parasites were defective in the upregulation of bradyzoite differentiation regulators BFD1 and BFD2 during stress-induced differentiation. Conditional overexpression of BFD1 or BFD2 rescued differentiation in ∆eIF1.2 parasites. We further show that eiF1.2 interacted with the yeast 40S ribosome and directed the scanning of a model 5’ untranslated region. Together, our findings imply that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish T. gondii chronic infection.
2024-04-10 | GSE245775 | GEO
Project description:Whole genome expression analyses between wild-type Mycobacterium tuberculosis H37Rv and the isogenic mprA::Kmr mutant. Expression analyses between these strains were conducted following growth under physiological conditions, or following exposure to non-inhibitory concentrations of SDS or Triton X-100.
2006-03-01 | E-MEXP-552 | biostudies-arrayexpress
Project description:Rotavirus NSP3 is a translational surrogate of the PABP-poly(A) complex for rotavirus mRNAs. To further explore the effects of NSP3 and untranslated regions (UTRs) on rotavirus mRNAs translation, we used a quantitative in vivo assay with simultaneous cytoplasmic NSP3 expression (wild-type or deletion mutant) and electroporated rotavirus-like and standard synthetic mRNAs. This assay shows that the last four GACC nucleotides of viral mRNA are essential for efficient translation and that both the NSP3 eIF4G- and RNA-binding domains are required. We also show efficient translation of rotavirus-like mRNAs even with a 5'UTR as short as 5 nucleotides, while more than eleven nucleotides are required for the 3'UTR. Despite the weak requirement for a long 5'UTR, a good AUG environment remains a requirement for rotavirus mRNAs translation.
| S-EPMC4699793 | biostudies-literature