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EIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast

ABSTRACT: eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast

OTHER RELATED OMICS DATASETS IN: GSE137021

PROVIDER: PRJNA423281 | ENA |

REPOSITORIES: ENA

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eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast

Project description:The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context, and AUG recognition stabilizes a closed PIC conformation. The unstructured N-terminal tail (NTT) of yeast eIF1A deploys five basic residues to contact tRNAi, mRNA, or 18S rRNA exclusively in the closed state. Interestingly, EIF1AX mutations altering the human eIF1A NTT are associated with uveal melanoma (UM). We found that substituting all five basic residues, and seven UM-associated substitutions, in yeast eIF1A suppresses initiation at near-cognate UUG codons and AUGs in poor context. Ribosome profiling of NTT substitution R13P reveals heightened discrimination against unfavorable AUG context genome-wide. Both R13P and K16D substitutions destabilize the closed complex at UUG codons in reconstituted PICs. Thus, electrostatic interactions involving the eIF1A NTT stabilize the closed conformation and promote utilization of suboptimal start codons. We predict UM-associated mutations alter human gene expression by increasing discrimination against poor initiation sites.

2017-12-21 | GSE108334 | GEO

eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast.

Project description: Not available

| S-EPMC5756025 | biostudies-literature

Virus-induced codon-specific reprogramming to favor viral RNA translation

Project description:How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in suboptimal codons remains a puzzling question. By integrating subcellular fractionation and transcriptome-wide analyses of translation in CHIKV-infected human cells, we demonstrate an unanticipated virus-induced reprogramming of the host translation machinery to favor translation of viral RNA over cellular genes featuring optimal codon usage. This reprogramming was specifically apparent at the endoplasmic reticulum (ER), the preferred translation compartment of CHIKV RNA, and it is mediated by the wobble uridine 34 tRNA modification enzyme KIAA1456 whose expression is enhanced upon viral infection. Since KIAA1456 itself is encoded by a CHIKV-like codon usage, infection triggers a positive feed-back loop that ensures efficient virus protein production. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to favor viral protein expression.

2022-06-17 | GSE143390 | GEO

Requirements for preinitiation complex formation in vivo

Project description:Requirements for preinitiation complex formation in vivo

| PRJNA506202 | ENA

Chromatin immunopreciptiation to determine the genome wide locatio of different components of the RNA polymerase II preinitiation complex in yeast

Project description:Genome wide location of different components of RNA polymerase II preinitiation complex in yeast S.cerevisiae

2008-06-01 | E-MEXP-1502 | biostudies-arrayexpress

Nucleosomes stabilize ssRNA-dsDNA triple helices in human cells

Project description:Nucleosomes stabilize ssRNA-dsDNA triple helices in human cells

| PRJNA473000 | ENA

Virus-induced codon-specific reprogramming to favor viral RNA translation

Project description:Virus-induced codon-specific reprogramming to favor viral RNA translation

| PRJNA600267 | ENA

Genome-wide regulations of the preinitiation complex formation and elongating RNA polymerase II by an E3 ubiquitin ligase, San1.

Project description:San1 is an E3 ubiquitin ligase involved in nuclear protein quality control via its interaction with intrinsically disordered proteins for ubiquitylation and 26S proteasomal degradation. Since a number of transcription/chromatin regulatory factors contain intrinsically disordered domains and can be inhibitory to transcription when in excess, San1 might be involved in regulation of transcription. To address this, we carried out ChIP-seq (Chromatin immunoprecipitation sequencing) here to analyze the role of San1 in genome-wide association of TBP (TATA-box binding protein that nucleates the preinitiation complex formation at the promoter for transcription initiation) and RNA polymerase II (that is recruited to the promoter by TBP and subsequently engaged in transcription elongation at the coding sequence for mRNA biosynthesis). Our results reveal the genome-wide role of San1 in facilitating the recruitment of TBP to the promoter, thus indicating its involvement in promoting the preinitiation complex formation for transcription initiation. Further, we find the global role of San1 in regulating RNA polymerase II at the coding sequence.

2021-12-04 | GSE190065 | GEO

Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples

Project description:This SuperSeries is composed of the following subset Series: GSE34577: Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples (training samples) GSE34714: Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples. (test samples) Refer to individual Series

2012-01-04 | E-GEOD-34823 | biostudies-arrayexpress

Requirements for preinitiation complex formation in vivo

Project description:Transcription by RNA polymerase (Pol) II requires assembly of a preinitiation complex (PIC) composed of general transcription factors (GTFs) bound at the core promoter. In vitro, the TATA-binding protein (TBP), TFIIB, TFIIF, and Pol II are essential for PIC formation and transcriptional initiation, whereas TFIIA, TFIIE, and TFIIH are not required under certain conditions. In addition, the PIC is stable in the absence of nucleotide triphosphates, and sequential addition of GTFs results in a series of partial PICs. Here, we analyze the roles of all GTFs in yeast cells by measuring PIC formation and Pol II transcription upon depletion of individual GTFs. All GTFs are essential for TBP binding and Pol II transcription in vivo, suggesting that partial PICs composed of GTF subsets do not exist at appreciable levels. In contrast, TBP-associated factors (TAFs) contribute to Pol II transcriptional activity at most (and perhaps all) genes, but TAF-independent transcription occurs at a substantial level, particularly at promoters lacking canonical TATA elements. Lastly, unlike the case in vitro, PICs are not observed in cells deprived of uracil, and presumably UTP, suggesting a mechanism that removes transcriptionally inactive PICs from promoters.

2019-02-27 | GSE122734 | GEO

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