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Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

ABSTRACT: Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

PROVIDER: PRJNA1180945 | ENA |

REPOSITORIES: ENA

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Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

Project description:Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

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Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

Project description:Mitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be effectively disrupted, leading to cell death and inhibition of tumor growth. However, challenges such as drug resistance remain significant in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts proceeds. Here, we demonstrate that mitotic cancer cells redistribute ribosomes toward the 5' untranslated region (5' UTR) and the start of the coding sequence (CDS), enhancing the translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). This mitotic induction of uORF/uoORF enriches the presentation of immunopeptides at the surface of cancer cells following treatment with mitotic inhibitors. Functional assays indicate the potential of such neoepitopes to provoke cancer-cell killing by T cells. Altogether, our findings highlight the therapeutic potential of targeting uORF/uoORF-derived neoepitopes in combination with mitotic inhibitors to enhance immune recognition and tumor cell elimination.

2025-06-30 | GSE280870 | GEO

Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

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Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells

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Budding yeast cohesin (Mcd1) distribution in mitotically arrested cells

Project description:genomic localization of the budding yeast cohesin complex was mapped in mitotically arrested cells by Mcd1 ChIP followed by hybridization to high-density tiled microarrays

2009-10-01 | GSE18021 | GEO

Budding yeast cohesin (Mcd1) distribution in mitotically arrested cells

Project description:genomic localization of the budding yeast cohesin complex was mapped in mitotically arrested cells by Mcd1 ChIP followed by hybridization to high-density tiled microarrays Cells were synchronized first in G1 and then released into media containing the microtubule poison nocodazole. Cells were fixed and processed for ChIP once arrested as large-budded cells. Immunoprecipitated DNA and total genomic DNA not subjected to immunoprecipitation were competitively hybridized to Nimblegen whole genome arrays.

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Genomic RNA-DNA duplexes in mitotically arrested cells

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A coding sequence-embedded principle governs translational reading frame fidelity

Project description:Upon initiation at an AUG start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. Although some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known how the ribosome normally prevents spontaneous frameshift errors. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3’ end of 18S rRNA to scan the AUG-like codons after the decoding process. The internal mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a post-decoding mechanism to safeguard the ribosome in the correct reading frame. Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors. Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes codon “stickiness”. Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes by minimizing the appearance of AUG-like codons in the frame 2. These results suggest an important layer of information embedded within the protein coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.

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Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo

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Temperature-dependent regulation of upstream open reading frame translation in s. cerevisiae

Project description:Temperature-dependent regulation of upstream open reading frame translation in s. cerevisiae

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